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Journal of Complementary and Integrative Medicine

Official Journal of the Natural Health Product Research Society of Canada

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Sprache: Englisch

Erstveröffentlichung: 1. Januar 2004

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Objective
The Journal of Comp lementary and Integrative Medicine (JCIM) focuses on evidence concerning the efficacy and safety of complementary medical (CM) whole systems, practices, interventions and natural health products, including herbal and traditional medicines.

JCIM is the official journal of the Natural Health Product Research Society of Canada. You can access the back issues of the Society's former Journal of Natural Health Product Research.

Topics
Quality, efficacy, and safety of natural health products, dietary supplements, traditional medicines and their synthetic duplica tes // Efficacy and safety of complementary therapies // Evidence-based medicine and practice, including evidence of traditional use // Curriculum development, educational system and competency of complementary health programs // Methodologies on research and evaluation of traditional medicin es and herbal products // Integrative medicine: basic and clinical research and practice // Innovation in CAM Curriculum // Educational Material Design

Article formats
Basic and Clinical Research Articles, Review Articles (Systematic, Scoping or very high-quality Narrative Reviews), Mini Review Articles, Discussion/Opinion Papers, Short Communications, Editorials

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Open Access
Ethics in the age of artificial intelligence: reflections from mapping the terrain and implications for traditional, complementary, and integrative medicine

22. April 2026

Jeremy Y. Ng

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Open Access
Chenopodium ambrosioides Linn. induces mitochondrial-dependent cell death via activation of mPT pore opening, caspases and apoptotic machinery

14. April 2026

Adeola Oluwakemi Olowofolahan, Mimidoo Gaaba, Fatima Bulus Musa

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Objectives Mitochondrion is an organelle involved in cellular energy generation and cell death. The mitochondrial permeability transition (mPT) pore plays a crucial role in the execution of mitochondrial-dependent cell death. Several medicinal plants evoke their therapeutic potential against tumor and cancer by instigating mitochondrial-dependent cell death. This research consequently explored the effect of chloroform fraction of Chenopodium ambrosioides (CFCA) on mitochondrial-dependent cell death via mPT pore. Methodology Rats were equally assigned into four groups; A (control), B (50), C (100) and D (200) mg/kg CFCA. Mitochondria were isolated by differential centrifugation. The mPT pore opening, mitochondrial ATPase (mATPase) activity and mitochondrial-lipid peroxidation (mLPO) were assessed spectrophotometrically. Caspases 9 and 3 levels, hepatic DNA fragmentation, histology and immunohistochemical analysis of Bax, Cytochrome c , P53 and anti-apoptotic Bcl-2 proteins were determined. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of CFCA was carried out. Results The CFCA dose-dependently induced mPT pore opening, enhanced mATPase activity, reduced malondialdehyde generation, increased Caspases 9 and 3 levels and effected hepatic DNA fragmentation. The histological assessment showed mild to moderate steatosis and infiltration of the hepatocytes. The CFCA upregulated the expression of Bax, Cytochrome c and P53 proteins while anti-apoptotic Bcl-2 protein was downregulated. The GC-MS analysis revealed the presence of certain pharmacologically reactive compounds including Tridecanoic acid, 12-methyl ester, Hexadecanoic acid methyl ester, 11-Octadecadienoic acid, methyl ester, Pyrido[2,3-d]pyrimidine and 6-Undecyl-5,6-dihydro-2H-pyran-2-one. Conclusions This study suggests the presence of phytochemicals in CFCA that could execute mitochondrial-mediated apoptosis via induction of mPT pore opening, caspases and apoptotic machinery.
Open Access
Antidepressant-like effect of Peperomia pellucida (L.) Kunth extract: analysis of behavioral and oxidative stress parameters in mice exposed to chronic unpredictable mild stress

13. April 2026

Fitrya Fitrya, Ghina Desfitriyana, Nyiayu Fauziyah Kurniawati, Vitri Agustiarini, Annisa Amriani, Rennie Puspa Novita

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Objectives Peperomia pellucida (Indonesian name: Suruhan) is a tropical plant easily found throughout Indonesia. This plant is used as a food ingredient and to treat various diseases due to its phytoconstituent content. This study aimed to evaluate the antidepressant effect of the ethanol extract of the Suruhan herb. Methods Mice were exposed to chronic mild stress using the chronic unpredictable mild stress (CUMS) method for 21 days, followed by a sucrose preference test. The antidepressant effect was assessed by behavioral changes in the tail suspension test (TST), forced swimming test (FST), and locomotor tests. Oxidative stress levels were measured using malondialdehyde (MDA) and catalase levels, and the evaluation was complemented by histopathological analysis. The antidepressant effect of the Suruhan extract (ES) was compared with that of normal controls, stress controls, and fluoxetine controls. Results In the behavioral test, there was no significant difference in immobility time and number of line crossings in the test group compared to the fluoxetine control (p>0.05). ES significantly increased the sucrose preference value of the test group. Oxidative stress parameter analysis showed that the extract reduced MDA levels in mice, no different from the fluoxetine control group (p>0.05), and increased catalase levels, but not as effectively as the standard drug (p<0.05). Histopathological analysis found a significant increase in the thickness of the granular layer in the dentate gyrus of mice treated with ES and fluoxetine compared to the stress group. Conclusions Suruhan herb has antidepressant-like effects and has the potential to be used as a functional food and complementary medicine in the treatment of depression.
Open Access
Black Maitake mushroom (Grifola frondosa) extract exerts anti-cancer effects and enhances the efficacy of chemotherapeutic drugs in 2D and 3D models of triple-negative breast cancer

8. April 2026

Silvia DeMarco, Sona Regonda, Siyaram Pandey

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Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that lacks hormone receptors and HER2 amplification, limiting targeted therapy options. Chemotherapeutics like cisplatin and taxol are commonly used but lack selectivity, often causing harsh side effects. These limitations have led to increased interest in natural health products (NHPs) as complementary treatments due to their potential anticancer benefits and lower toxicity. Black Maitake mushroom ( Grifola frondosa ), used in traditional Chinese medicine, contains polysaccharides with reported anticancer activity. However, further research is needed on the whole extract, its mechanism, and its interaction with chemotherapy. Objectives This study assessed the anticancer effects of Black Maitake Odaira Extract – Prothera (BMOE; manufactured by Shogun Maitake Canada, London, ON) on the MDA-MB-231 TNBC cell line. BMOE was evaluated alone and in combination with chemotherapeutic agents cisplatin and taxol using both 2D and 3D in vitro models. Methods Apoptosis was evaluated using Hoechst 33342, Annexin V, and propidium iodide staining. Mitochondrial membrane depolarization was assessed via TMRM. A wound-healing assay measured cell migration. Structural effects were examined in 3D spheroid cultures following treatment. Results BMOE induced dose- and time-dependent apoptosis and mitochondrial depolarization. In 3D models, BMOE disrupted spheroid structure. The wound-healing assay showed impaired TNBC cell migration. Most importantly, BMOE significantly enhanced chemotherapeutic efficacy when combined with cisplatin or taxol. Conclusions These findings highlight the potential of BMOE as a non-toxic adjunct that enhances the efficacy of standard chemotherapies to contribute to the development of safer, more targeted treatment strategies for TNBC.
Open Access
Retraction of: Evaluation of the protective effect of the Echinacea Purpurea against apoptosis and inflammation induced by overdose of iron dextran on the hematopoietic system

7. April 2026

Doaa Kahim Abdul Ridha, Ali Faris Hassan

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Hydroethanolic root extract of Ficus capensis exhibits antiulcerogenic activities in acetic acid-induced colitis rat model

7. April 2026

George Owusu, Meshack Antwi-Adjei, Yeboaba Kofi Opoku-Yeboah, Barnabas Tuatil, Abigail Adu-Boateng, Frederick Emmanuel Baidoo, Francis Kwame Abrokwah, Benjamin Aboagye

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Objectives Ficus capensis (FCE) is widely used in Ghana and some other West African countries to treat gastrointestinal diseases. This study examines the antiulcerogenic properties of the ethanol-based FCE root extract in rats using acetic acid-induced ulcerative colitis model. Methods Rats were arbitrarily assigned to 6 groups (n=5) and given either oral normal saline (10 mL/kg), sulfasalazine (500 mg/kg), or FCE (30, 100, and 300 mg/kg) for 7 days. To induce colitis, 500 μL of acetic acid (4 % v/v) was given intrarectally on day 2. On the 8th day, rats were euthanized. Hematology, antioxidant, and histopathological investigations were assessed. Results FCE significantly prevented body weight loss and reduced the colon weight/length ratio to 0.106 ± 0.004 g/cm relative to the control. Additionally, FCE reduced DAI to 2.035 ± 0.1216 compared to the control. The histopathology showed that FCE-treated colons reduced inflammatory scores compared to the control. Levels of NF-κB and TNF-α, gross colonic damage and epithelial cell loss were reduced. FCE elevated colonic SOD and CAT activity to 12.60 ± 1.327 and 9.60 ± 0.6713, correspondingly. Furthermore, the amount of MDA decreased to 29.72 ± 1.974 compared to the control. FCE increased levels of RBC and HGB, respectively, to 8.64 ± 0.48 (×10 6 /µL) and 9.36 ± 0.62 g/dL and lowered WBC and NEU to 10.27 ± 0.36, 9.35 ± 0.62, 20.43 ± 0.82, and 18.47 ± 0.47, respectively, compared to the control. Conclusions Hydroethanolic root extract of FCE possesses antiulcerogenic effects.
Open Access
Successful integration of Yoga and Naturopathy with conventional medicine for health promotion: insights from the Tamil Nadu model in rural India

6. April 2026

Vaishnu Karthik Kamaraj, Srikaren Udhayakumar, Yeswanth Kumaran Venkatachalam, Poornima Ravi, Maheshkumar Kuppusamy

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Open Access
Chromatographic analysis of Crataegus azarolus and possible psychiatric implications

20. März 2026

Bekir Nihat Dogrul, Ibrahim Kiliccalan, Ekrem Samet Asci

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Background Crataegus azarolus (hawthorn) is a medicinal plant traditionally used for various health benefits and culinary reasons, although its psychiatric effects remain poorly studied. This study aimed to assess the volatile chemical composition and ionic profile of C. azarolus , and to integrate these findings with a targeted review of the literature to propose potential psychiatric implications. Methods Methanolic extracts of dried flowers, leaves, and berries were analyzed by gas chromatography–mass spectrometry (GC–MS), with compounds identified using reference libraries. Ion chromatography (IC) with anion and cation columns was used to quantify inorganic ions, expressed as mg per 100 g dried material. Results GC–MS tentatively identified 13 major compounds, including flavonoids, fatty acids, sterols, vitamin D derivatives, and digitoxin. Many of these constituents have been suggested having anti-inflammatory, antioxidant, anxiolytic, and antidepressant-like activities in preclinical studies. Among the compounds, the flavonoids quercetin and lucenin-2 were particularly notable due to their proposed roles in central nervous system function, neuroprotection and possible psychiatric effects. IC analysis additionally revealed the presence of various inorganic ions, although their overall concentrations were low. Conclusions The biochemical complexity of C. azarolus highlights its potential relevance for mental health, yet direct preclinical and clinical evidence remains lacking. Future investigations are needed to clarify its psychiatric applications.
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Neuroprotective role of Bougainvillea spectabilis in ketamine-induced neurotoxicity: targeting oxidative stress and neuroinflammation

20. März 2026

Rania Elgohary, Omar M.E. Abdel-Salam, Eman R. Youness, Enayat A. Omara, Amany A. Sleem

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Objectives Schizophrenia is a persistent and devastating mental illness that affects around 1 % of the population. Despite the availability of antipsychotic drugs, their limited efficacy and significant adverse effect profiles have sparked an increased interest in finding well-tolerated, safer alternatives. Recently the bioactive compounds that are produced from natural sources as possible supplementary therapy to reduce the symptoms of schizophrenia. This study seeks to evaluate the potential therapeutic effects of Bougainvillea spectabilis (B. spectabilis) in alleviating oxidative stress and neuroinflammatory pathways associated with ketamine-induced biochemical and histopathological changes. Methods Rats were administered ketamine (30 mg/kg, s.c.) to cause neurotoxicity. B. spectabilis extract at dosages of 50 and 100 mg/kg, were administrated 30 min later. Results B. spectabilis extract significantly decreased oxidative stress, including homocysteine and malondialdehyde (MDA), while increasing endogenous antioxidant defenses such as reduced glutathione (GSH) and folic acid levels. The extract also attenuated neuroinflammatory responses through downregulation of TNF-α and NF-κB expression and markedly improved the histopathological architecture of brain tissue. Conclusions The study demonstrates that B. spectabilis extract exerts neuroprotective effects through antioxidant and anti-inflammatory mechanisms. These findings suggest that the extract may represent a promising adjunct therapeutic strategy for mitigating neurotoxicity associated with oxidative stress and neuroinflammation.
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Serum TNF-α, oxidized LDL, and APOCII as novel predictors for familial mediterranean fever in Egyptian children: a cross-sectional study

19. März 2026

Hala T. El- Bassyouni, Khaled Hamed, Eman Refaat Youness, Hisham A. Orban, Abeer Selim, Ahmed Adel, Rehab S.I. Moustafa, Randa Salah Lotfy, Maha Mahmoud A. Kobesiy, Mina Wassef Girgiss, Sherif H. Elwan, Hanan Farouk, Ramy Mohamed, Hanaa Reyad Abdallah, Moushira Zaki

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Persistent subclinical inflammation is a hallmark of familial Mediterranean fever (FMF), the most common autoinflammatory disease. Among the key mediators implicated in this chronic inflammatory state are tumor necrosis factor-alpha (TNF-α), oxidized low-density lipoprotein (OxLDL), and apolipoprotein C-II (APOC2), which contribute to the dysregulated immune response characteristic of FMF. The present study aims to evaluate the potential role of TNF-α, OxLDL, and APOC2 as diagnostic biomarkers of disease severity in patients with FMF. Methods The study enrolled 66 patients diagnosed with FMF and 60 age- and gender-matched healthy controls. Serum levels of tumor necrosis factor-alpha (TNF-α) and oxidized low-density lipoprotein (OxLDL) were quantified using the enzyme-linked immunosorbent assay (ELISA) technique. However, the apolipoprotein C-II (APOC2) concentrations were measured using an automated biochemistry analyzer. Furthermore, the Carotid intima media was assessed. Results Serum TNF-α levels were significantly higher in FMF patients than in the control group, emphasizing the protein’s role as an important marker of chronic inflammation. Levels of low-density lipoprotein (OxLDL) and apolipoprotein C-II (APOC2) were also notably altered in the FMF cohort. Notably, OxLDL, APOC2 and TNF-α demonstrated strong positive correlation with attack frequency, multiple linear regressions analysis showed that OxLDL (β=1.53, p=0.002) and TNF-α (β=1.38, p=0.003) were significant predictors for higher number of attacks, suggesting their potential role involvement in the inflammatory cascade and their utility as complementary biomarkers in FMF. The carotid intima-media thickness (CIMT) of patients and control subjects did not differ statistically significantly. Conclusions TNF-α, oxidized LDL, and APOC2 are key pro-inflammatory mediators that may serve as novel biomarkers for assessing chronic inflammatory status in FMF patients. Their elevated levels could provide valuable insights into disease progression and help guide personalized treatment strategies.
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The Journal of Complementary and Integrative Medicine is switching its publication model to open access

18. März 2026

Suzanne Mekking, Jeremy Y. Ng

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In Silico evaluation of bioactive compounds as potential inhibitors targeting HIF-1α/VEGFA/BACE1 pathway against Alzheimer’s disease

25. Februar 2026

Sakshi Rai, Suman Kumar Ray, Sukhes Mukherjee

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Background Neurodegenerative disorders such as Alzheimer’s disease (AD) are characterized by progressive neuronal degeneration, predominantly caused by the accumulation of amyloid-beta (Aβ) and neuroinflammatory processes. Hypoxia, characterized by diminished oxygen levels, intensifies these mechanisms by stimulating hypoxia-inducible factor 1-alpha (HIF-1α), potentially enhancing BACE1 enzyme activity and resulting in increased Aβ synthesis and render neurons especially susceptible to hypoxia, exacerbating disease progression. Existing therapies are constrained by inadequate medication distribution across the blood-brain barrier and associated adverse effects. Objectives This study aims to identify potential therapeutic agents targeting HIF-1 α , VEGFA, BACE1 key molecules involved in AD by exploring neuroprotective effects of bioactive compounds like benzyl isothiocyanate (BITC), Aurantiamide Acetate (AA), and galantamine, with the goal of developing more effective, targeted treatments. Methodsology We used in silico screening, such as molecular docking and ADMET analysis, to assess the binding affinity, pharmacokinetics, and toxicity of potential inhibitors, followed by in vitro testing. Results and discussion Results identified several compounds with strong binding affinities and favorable ADMET profiles as potential inhibitors of HIF-1 α , VEGFA, BACE1 and experimental data support that hypoxia, via HIF-1α, upregulates BACE1, increasing Aβ production and contributing to AD. Targeting these pathways may offer a multi-faceted approach to therapy, reducing neuroinflammation and amyloid pathology. Conclusions In silico screening of potential molecules across different pathogenic pathways in Alzheimer’s disease shows promise in developing successful therapeutic methods and continued validation may result in more tailored and safer medicines that address underlying neurodegenerative pathways.
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The effects of aromatherapy in children: a systematic review and a call for research in autism

19. Februar 2026

Leonardo Ribeiro Miedes, Edinaldo Siqueira Souza, Thais Miriã da Silva Santos, Matheus Silva Fornel, Kátia Bilhar Scapini, Iris Callado Sanches, Camilla de Paula Pereira Uzam, Juliana Monique Lino Aparecido, Nathalia Bernardes

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Introduction Aromatherapy, the therapeutic use of essential oils, is a growing complementary practice in pediatric care. This systematic review analyzed the scientific evidence on its application and effects in children, with a secondary aim of exploring its use for children with autism spectrum disorder (ASD). Content Following the PRISMA guidelines, the screening was carried out in Rayyan by two researchers, with studies from the PubMed, Cochrane Library, BVS Library and Web of Science databases, including only clinical trials. The risk of bias assessment used the Cochrane RoB 2 tool. Summary Out of 1,089 identified studies, seven randomized controlled trials were included. The literature was predominantly focused on neurotypical children, revealing that acute inhalation of essential oils (mainly lavender and orange) was used for managing anxiety in specific settings, particularly dentistry. Findings showed a trend towards reduced anxiety and pain scores, alongside decreased heart rate. However, significant methodological heterogeneity and small sample sizes were noted. The secondary aim highlighted a pronounced evidence gap: only one small-scale study included children with ASD, which reported no significant benefits of aromatherapy. Outlook Preliminary evidence suggests potential benefits of aromatherapy for anxiety in neurotypical children within controlled contexts. However, the evidence base is limited and insufficient for robust clinical guidance. A critical scarcity of research exists on aromatherapy for children with ASD, underscoring the need for more rigorous and adequately powered future studies.
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Black maitake induces apoptosis and enhances the efficacy of standard chemotherapy in 2D and 3D U-87 MG glioblastoma cell models

17. Februar 2026

Sona Regonda, Victoria Iannetta, Hannah Drew, Siyaram Pandey

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Glioblastoma is an aggressive primary brain tumor marked by rapid growth, invasiveness, poor prognosis, and an over 90 % tumor recurrence rate. Current radiation and chemotherapy treatments are limited by non-selectivity and toxicity, creating a need for safer complementary treatments. Historically, natural health products (NHPs) have been used medicinally across cultures for their anti-inflammatory and antioxidant effects. More recently, they have gained recognition for their selective, non-toxic properties in cancer treatment, suggesting their potential as adjuncts to conventional therapies. Objectives Black maitake ( Grifola frondosa ) extract, a well-tolerated NHP with known immunomodulatory properties, has demonstrated anticancer effects in breast cancer models. This study investigates the ability of Black Maitake Odaira Extract – Prothera (BMOE; a trade name of the extract manufactured by Shogun Maitake Canada, London, ON) to induce cell death in the U-87 MG glioblastoma cell line using 2D and 3D models, alone and in combination with the standard chemotherapy: temozolomide (TMZ). Methods Apoptosis was assessed via Hoechst 33,342, annexin V, and propidium iodide staining, along with morphological analyses. Mitochondrial depolarization was measured using TMRM, cell migration was assessed via wound-healing assays, and structural integrity was evaluated using 3D spheroids. Results BMOE, alone and with TMZ, induced dose-dependent apoptosis, mitochondrial depolarization, and impaired glioblastoma cell migration. BMOE also disrupted 3D spheroid structures and promoted nuclear condensation, consistent with apoptotic processes. Most notably, BMOE significantly enhanced the anti-cancer effects of TMZ. Conclusions These findings support the potential of BMOE as a complementary therapy that enhances the efficacy of current glioblastoma treatments.
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Exploring the immunomodulatory activities of Scoparia dulcis extract against lipopolysaccharide-induced allergic inflammation in mice through suppression of innate pro-inflammatory cytokines, COX-2 and iNOS signalling pathways

13. Februar 2026

Jones Ofori-Amoah, Cynthia Amaning Danquah, Kwesi Boadu Mensah, Meshack Antwi-Adjei, Reuben Ayivor-Djanie, Abigail Hohoayi, Aaron Opoku Antwi, Sylvester Yao Lokpo

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Objectives This study sought to evaluate the biological effects of the hydroethanolic extract of Scoparia dulcis (SDE) on some innate immune responses that are implicated in inflammatory respiratory diseases, using the lipopolysaccharide-induced mice model. Methods Lipopolysaccharide (LPS, 0.5 mg/kg) was dissolved in 2 mL phosphate buffered saline and injected (IP) into mice 1 h after drug administration to induce inflammation and systemic immune responses. Mice were pre-treated with either 10 mg/kg prednisolone or SDE (50, 100, 250 mg/kg, p . o .). The expressions of TNF-α, IL-1β, IL-6, stem cell factor (SCF), nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 enzymes (COX-2) were evaluated by a real-time PCR technique. Furthermore, histopathological examinations were performed on the lung tissues. Results Pre-treatment with SDE significantly suppressed ( p <0.001) the expressions of TNF-α, SCF, IL-1β, IL-6, and COX-2, as well as iNOS enzymes in the mRNAs of LPS-induced mice, and it also reduced NO levels and endotoxin-induced lung damage. Conclusions SDE exhibited strong immunomodulatory activities and thus, would have potential benefits in immune-inflammatory disease management.
Open Access
Investigation of the therapeutic effects of medicinal leech treatment on lower extremity ischemia–reperfusion injury

30. Januar 2026

Kübranur Ünal, Başak Samur, Annahda Sharif, Leyla İbrahimkhanli, Nihat Yumuşak

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Objectives This study aims to investigate the therapeutic effects of medical leech treatment (MLT) on ischemia/reperfusion (I/R) injuries in the lower extremities of rats. Methods A total of 18 Wistar Albino rats were used and randomly assigned to three groups: Sham (n=6), I/R (n=6), and MLT (n=6). The I/R group rats underwent I/R induction in the femoral artery using an atraumatic vascular clamp. The same was done for the MLT group, after which MLT was carried out on the gastrocnemius muscle region of each rat. Histopathological analysis of the tissue and biochemical analysis was performed on the serum and tissue samples of the rats of each group. Results According to the histopathological analysis, the scores of edema, degeneration, necrosis and inflammation of the MLT group were significantly lower than the I/R group (p<0.001). In the tissue and serum biochemical analysis, no statistically significant differences were detected among groups for Interleukin-6 (IL-6), Superoxide Dismutase (SOD), Calcitonin Gene-Related Peptide (CGRP), Nitric Oxide (NO), Tumor Necrosis Factor-α (TNF-α), Hypoxia-Inducible Factor-1α (HIF-1α), Ischemia-Modified Albumin (IMA), Glutathione Peroxidase (GPx), Catalase (CAT) and Endothelin-1 (EDN-1) levels. Conclusions Although biochemical analysis results showed no significant differences among the groups, the histopathological analysis suggests notable clinical therapeutic effects of MLT in I/R models. Further research is warranted to substantiate these findings.
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Evaluation of the protective effect of the Echinacea Purpurea against apoptosis and inflammation induced by overdose of iron dextran on the hematopoietic system

26. Januar 2026

Doaa Kahim Abdul Ridha, Ali Faris Hassan

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Objectives Investigate the cytoprotective, anti-apoptotic, and anti-inflammatory effects of two different doses of Echinacea purpurea extract against iron overload-induced bone marrow suppression and spleen cell damage. Methods 50 male rats divided into five groups: (I) received a 0.2 mL intraperitoneal saline injection, 1 mL oral gavage daily. (II) intraperitoneally injected (200 mg/kg iron); daily oral gavage 1 mL saline solution. (III) intraperitoneally injected (200 mg/kg iron), E. purpurea (100 mg/kg/day) orally administered. (IV) intraperitoneally injected (200 mg/kg iron), E. purpurea (200 mg/kg/day) orally administered. (V) intraperitoneally injected (200 mg/kg iron), orally administered vitamin E (200 mg/kg/day). Injections administered every 3 days; treatment for 4 weeks. Results Echinacea Purpurea significantly reduces monocyte cell count, Akt1, Foxo-1, and NFκB; significantly elevates lymphocyte cell count; and highly significantly elevates Sirt-3 gene expression. It substantially reduces the levels of IL-6, MCP-1, and FasL. Conclusions Echinacea Purpurea exhibits anti-inflammatory and immunomodulatory effects, and it reduces bone marrow suppression and spleen cell injury caused by iron overload.
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From ancient remedy to modern COVID-19 adjunct: a narrative review of mechanistic, in vitro, and clinical evidence on propolis

19. Januar 2026

Giorgos Tzigkounakis, Jonathan Brown

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Introduction Despite the global rollout of COVID-19 vaccines, limited access, vaccine hesitancy, and the emergence of viral variants continue to underscore the need for complementary antiviral strategies. Propolis, a resinous bee product widely used in traditional medicine, has attracted scientific interest due to its reported antiviral, anti-inflammatory, immunomodulatory, and antioxidant properties. Content This narrative review examines the therapeutic potential of propolis as a candidate adjunctive treatment for COVID-19, focusing on mechanistic, in vitro, and clinical evidence. A comprehensive review was conducted using PubMed, Scopus, and Europe PMC (January 2020 to May 2025), covering molecular docking reports, in vitro assays, and human clinical studies evaluating propolis or its key constituents against SARS-CoV-2. In silico reports describe interactions of more than forty propolis constituents with key host and viral targets, providing mechanistic context. In vitro evidence demonstrates inhibition at entry and replication targets alongside attenuation of inflammatory signaling. Limited clinical data, spanning seven studies and two case reports, suggest milder symptoms and shorter hospital stays, with no serious adverse events observed. Summary and Outlook Preclinical and early clinical evidence suggest propolis may be a useful adjunct in COVID-19 therapy. Large, placebo-controlled trials with well characterized and standardized extracts are needed to confirm efficacy and safety.
Open Access
Natural Health Products Research Society of Canada Natural Health Products, Probiotics & Neurodegeneration Online Symposium 2025

19. Januar 2026

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Methoxy flavonoids inhibits proliferation and induces apoptosis of A549 lung cancer cells

1. Januar 2026

Dhirendra Singh, Amit Kumar, Inderjeet Verma, Govind Yadav, Sanket Shukla

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Objectives Lung cancer is one of the most common malignancies and the leading cause of cancer-related mortality worldwide, posing a major public health challenge. Flavonoids, a large and diverse group of plant metabolites, exhibit various anticancer properties, making them promising candidates for therapeutic applications. This study evaluated the anticancer efficacy of methoxy flavonoids and elucidated their underlying mechanisms of action in A549 lung cancer cells. Methods A549 cells were treated with various flavonoids (AKC1–AKC5), and their effects were analyzed using an MTT assay, DAPI staining, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, colony formation, and wound scratch tests. Molecular docking was also performed to confirm the binding of AKC1 and AKC3 to EGFR, BCL-2, and CDK-2 proteins. Results AKC1 and AKC3 prevented the growth of A549 lung cancer cells with IC50 of 64.57 and 19.80 μM among 5 methoxy flavonoids. AKC1 and AKC3 triggered notable alterations in the shape and reduced the colony-forming potential of A549 cells. The DAPI staining experiment demonstrated that AKC1 and AKC3 impede the growth of cancer cells through activation of apoptotic cell death. Moreover, the anticancer properties of AKC1 and AKC3 were attributed to significant inhibition of MMP and a notable ROS enhancement in a dose-related pattern. The wound scratch assay demonstrated that AKC1 and AKC3 suppressed A549 lung cancer cell migration, suggesting their anti-metastatic properties. Molecular docking studies confirmed that AKC-1 and AKC-3 bind strongly to EGFR, BCL-2, and CDK2, suggesting a multi-target mechanism that underlies their anti-proliferative and pro-apoptotic effects in A549 cells. Conclusions AKC1 and AKC3 exhibited significant anticancer activity against A549 cells and may serve as promising therapeutic drugs for lung cancer treatment.
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The effect of ethanolic extract Panax ginseng roots on hypothyroidism-induced memory impairment, inflammation, and hippocampal tissue oxidative damage in rats

30. Dezember 2025

Hedyeh Askarpour, Mahdiyeh Hedayati-Moghadam, Faezeh Mirzaee, Sobhan Eslami, Yousef Baghcheghi

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Objectives Panax ginseng is rich in ginsenosides, which possess antioxidant, anti-inflammatory, and neuroprotective effects. This study aimed to evaluate the effects of ethanolic extract P. ginseng roots (GSNG) on memory deficits, inflammation, and oxidative damage in the hippocampal tissue of male rats subjected to hypothyroidism. Methods Male Wistar rats were divided into four groups: Control, PTU, PTU-GSNG 50 (50 mg/kg), and GSNG100 (100 mg/kg). Over 42 days, PTU was provided in drinking water at a concentration of 0.05 %. GSNG was administered via gavage during the PTU treatment and throughout the behavioral testing phase. In fifth week the behavioral tests including water maze and shuttle box were conducted. After 42 days, hippocampal tissues were harvested post-euthanasia for analysis of oxidative stress markers and interleukin-6. Results Administration of GSNG significantly ameliorated memory impairment and reduced oxidative damage and inflammation in the hippocampus of hypothyroid rats. Behavioral assessments using the water maze and shuttle box indicated marked improvements in memory impairment induced by hypothyroidism (p<0.01 and p<0.001). Biochemical analyses revealed significant modulation of oxidative stress markers, including MDA, total thiol groups, SOD activity, catalase levels, and interleukin-6, with both doses of Ginseng demonstrating beneficial effects. Notably, the higher dose (100 mg/kg) exhibited superior efficacy compared to the lower dose (50 mg/kg) across all measured parameters. Conclusions The findings suggest that P. ginseng effectively mitigates hypothyroidism-induced memory impairment by attenuating oxidative stress and neuroinflammation, highlighting its potential as a therapeutic agent for cognitive deficits associated with thyroid dysfunction.
Open Access
Patient experiences and perspectives regarding medicinal cannabis: a qualitative scoping review

29. Dezember 2025

Frederik Rosenbæk, Jesper Bo Nielsen, Line Bjørnskov Pedersen, Sif Schmidt Stewart-Ferrer, Jens Søndergaard, Jessica Joan Williams, Elisabeth Assing Hvidt

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Introduction The objective was to synthesise existing qualitative research on patients’ experiences and perspectives regarding medicinal cannabis and cannabis-based prescription medications. Content A systematic search of EMBASE, Scopus, PubMed, and the Cochrane Library identified peer-reviewed articles. Characteristics and findings were organised using a predesigned data charting form. Thematic analysis identified key themes. Reporting followed PRISMA-ScR guidelines. Summary From 849 records, 40 met inclusion criteria. Themes highlighted therapeutic potential and tolerability across various conditions. Patients described diverse administration methods and dosing strategies tailored to individual needs. Barriers included stigma, high costs, and bureaucratic delays in access and reimbursement. Facilitators involved support from healthcare providers, family, peers, and communities. Patients expressed a need for more education, information, and research. Many viewed prescription cannabis as superior to conventional medicines, though concerns about safety persisted. Outlook A gap exists between generally positive patient-reported experiences and the cautious stance of the medical community, which calls for more definitive research. Patients often face stigma and bureaucratic hurdles, though support from physicians and social networks can ease access. Views on safety and effectiveness vary, as some see medicinal cannabis as natural and safe, while others remain sceptical.
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Effects of resveratrol on CYP450-derived arachidonic acid metabolites and mRNA gene expression in human endothelial HUVEC cells

23. Dezember 2025

Yazun Bashir Jarrar, Mansour Al-Sayed Ahmad, Arwa Althaher, Wesam Nasser, Fatima Khirfan, Ala’a S. Shraim, Su-Jun Lee

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Objectives This study aims to investigate the expression of arachidonic acid (ARA)-metabolizing cytochrome P450 (CYP450) enzymes and their metabolites, as well as the effects of resveratrol, a compound known for its cardiovascular benefits, on these enzymes in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were cultured and treated with 10 µM resveratrol for 24 h. The mRNA expression of key ARA-metabolizing CYP450 enzymes was analyzed using real-time polymerase chain reaction. ARA metabolites produced by CYP450s were identified and quantified in cell culture media and lysates using liquid chromatography coupled with mass spectrometry. In addition, in silico docking was done to evaluate the effect of resveratrol on the identified CYP450s in HUVECS. Results CYP2J2, CYP2U1, and epoxide hydrolase were expressed in HUVECs; however, their mRNA expression levels were not significantly altered following resveratrol treatment. The metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) and its synthesizing CYP450 genes were not detected or below the lower limit of detection in HUVECs. Additionally, several epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETEs) were present in significantly higher amounts in the cell culture media compared to the cell lysates. Resveratrol treatment significantly reduced (p<0.05, t-test) the levels of EETs and DHETEs. In addition, in silico analysis showed resveratrol has a moderate affinity to interact with CYP2J2, the major EETs producer. Conclusions These findings suggest that resveratrol significantly reduces the levels of EETs and DHETEs possibly through direct interaction with CYP2J2. Furthermore, HUVECs may not be a suitable in vitro model for studying ARA metabolism to 20-HETE.
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Avocado oil protects the gastric tissue in favism from oxidative stress, inflammation, and apoptosis

22. Dezember 2025

Khaled M. M. Koriem, Safaa M. N. El-Gammal

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Objectives Favism is a severe hemolytic anemia, while avocado oil has anti-inflammatory and antioxidant properties. The objective is to determine if avocado oil can improve blood parameters, liver function, gastric antioxidants, inflammatory cytokines, and the apoptotic genes p53 and bcl-2 in favism-induced rats. Methods Thirty-six male albino rats were divided into two main (normal and favism-induced) groups. Normal group (18 rats/group) subdivided into three subgroups (6 rats/group); control, avocado oil (1.5 mL/rat)-treated, and avocado oil (3 mL/rat)-treated subgroups: normal rats orally administrated once with 1 mL distilled water/rat, 1.5 mL of avocado oil/rat, and 3 mL of avocado oil/rat, respectively. Favism-induced group (18 rats/group) subdivided into three subgroups (6 rats/group); Favism, avocado oil (1.5 mL/rat) + favism, and avocado oil (3 mL/rat) + favism; favism-induced rats orally administrated once with 1 mL distilled water/rat, 1.5 mL of avocado oil/rat, and 3 mL of avocado oil/rat, respectively prior to favism induction. Results Favism reduced blood parameters, liver function, gastric NADPH oxidase, glutathione peroxidase, catalase, superoxide dismutase, interleukin-10, and ATPase levels but increased gastric malondialdehyde, conjugated dienes, oxidative index, tumor interleukin-1β, interleukin-6, nuclear factor kappa B values, and necrosis factor-α compared to the control group in the male rats that were induced with favism. After four weeks of oral administration of avocado oil, all of these measures approached control levels in favism-induced rats, suggesting that a higher dose was more beneficial than a smaller one. Conclusions Avocado oil improved blood parameters, liver function, gastric antioxidants, inflammatory cytokines, and the apoptotic genes p53 and bcl-2 in favism-induced rats. These findings indicate that avocado oil may help reduce gastric damage associated with favism by lowering oxidative stress and inflammation, suggesting a need for further clinical investigation.
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Interoception and eating behavior in participants at risk for hypertensive disorders of pregnancy

18. Dezember 2025

Naomi Deokule, Ghada Bourjeily, Anna Palatnik, Nina K. Ayala, Nicole R. Nugent, Amanda Desmarattes, Margaret H. Bublitz

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Objectives Disordered eating during pregnancy can impact maternal and fetal health. Disordered eating has been linked to higher cardiovascular risks including hypertensive disorders of pregnancy (HDP). Interoceptive awareness, the ability to perceive and respond to bodily sensations, is reduced among people with disordered eating and may be associated with blood pressure (BP). This study tested these associations in pregnant women at risk for HDP. Methods Ninety-five pregnant women at risk for HDP participated in the study. At ∼18 weeks’ gestation we measured 24-hour BP, interoceptive awareness, and disordered eating. Linear regression analyses were used to test associations, adjusting for covariates (BMI, education, income, race). Results Greater interoceptive awareness—specifically lower anxiety about bodily sensations (“Not Worrying”)—was significantly associated with lower daytime diastolic BP (B=–0.21, p=0.05), lower uncontrolled eating (B=–0.52, p<0.001), and lower emotional eating (B=–0.51, p<0.001). Higher scores on the “Not Worrying” subscale were associated with less Uncontrolled Eating (B=−0.52, p<0.001) and less Emotional Eating (B=−0.51, p<0.001). Higher scores on the “Attention Regulation” subscale were associated with less Uncontrolled Eating (B=−0.24, p=0.02) and less emotional eating (B=−0.25, p=0.02). Cognitive Restraint was associated with higher nighttime diastolic BP (B=0.27, p=0.04) but not interoceptive awareness. Conclusion Increased interoceptive awareness was associated with both healthier eating behaviors and lower BP in pregnant women at risk for HDP. Interventions that enhance interoceptive awareness may offer a promising strategy for reducing risk for cardiovascular complications in pregnancy.
Open Access
Guava (Psidium guajava L.) leaf extract improves the prognosis of nonalcoholic fatty liver and biochemical parameters in rats with metabolic syndrome

18. Dezember 2025

Eduardo Rivadeneyra-Domínguez, Socorro Herrera-Meza, María F. Almanza- Domínguez, Héctor G. Acosta-Mesa, Daniel Hernández-Baltazar, Isaac Zamora-Bello, Juan F. Rodríguez-Landa

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Objectives To evaluate the effects of chronic oral administration of commercial guava ( Psidium guajava L.) leaf extract on biochemical markers and liver histology in a model of metabolic syndrome in rats. Methods 35 Wistar rats were assigned to five independent groups (n=7 per group): the control group (CG), which received a diet with standard rodent food (Nutri-Cubos ® ) and water ad libitum ; the metabolic syndrome group (MS), MS + P . guajava (Pg) low-dose (PgL; 100 mg/kg), MS + Pg medium-dose (PgM; 200 mg/kg), and MS + Pg high-dose (PgH; 300 mg/kg) groups. MS was induced with a rich diet of fat and carbohydrates, in addition to the intake of a 30 % sucrose solution ad libitum for 14 weeks. From week 15 onward, guava leaf extract or vehicle was administered orally every 24 h for 30 consecutive days without changing the experimental diet. At the end of the treatment, biochemical tests, liver histopathological analysis and adipose tissue analysis were performed. Results The MS group presented levels above the reference ranges for biochemical tests, weight gain, waist circumference gain, arterial hypertension, atypical liver cells and aberrant appearance in adipose rat tissue. The PgM and PgH groups presented opposite effects of MS on biochemical parameters, such as increased blood pressure and liver damage. Conclusions Chronic treatment with Pg leaf extract attenuated MS in Wistar rats, restoring the levels of biochemical parameters and exerting hepatoprotective effects. These findings suggest that guajava extract could be used in the development of therapeutic agents to improve the biochemical and histological alterations induced by MS.
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Traditional formulation-Vanari Gutika treatment improves the testosterone biosynthesis and sperm quality in adult male mice

12. Dezember 2025

Arti Rajpoot, Anupam Yadav, Shubhanshu Yadav, Nikita Nikita, Neha Dhar Dubey, Gyaneshwer Chaubey, Raghav Kumar Mishra

Artikelnummer: 20250305

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Objectives Vanari Gutika (VG), an Indian traditional formulation containing Mucuna pruriens as a principal component, is traditionally used for the management of male reproductive disorders. However, there is a significant lack of evidence-based research validating its effects on male fertility and testosterone biosynthesis. This study aimed to investigate the impact of VG on testicular steroidogenesis, lipid peroxidation, and sperm quality in male mice. Methods Adult male mice were orally administered VG at 75, 150, or 300 mg/kg body weight/day for 35 days. Testicular function was assessed through sperm morphology and viability, lipid peroxidation and expression of key steroidogenic and oxidative stress-related proteins. Results VG at 150 and 300 mg/kg significantly increased testis weight and serum testosterone, with a concurrent reduction in estradiol. VG (150 mg/kg) improved normal sperm morphology and reduced abnormalities. Markers of oxidative stress status improved, evidenced by reduced LPO and increased Nrf-2 expression. VG treatment enhanced the expression of steroidogenic markers (SF-1, CYP11A1, 3β-HSD, StAR, and 17β-HSD) at higher doses. Conclusions Higher doses of VG (150 and 300 mg/kg BW) promote testicular androgenesis, reduces oxidative stress, and improves sperm quality. Consequently, our results provide robust and compelling evidence supporting its potential as a dietary supplement for boosting the testosterone level and sperm quality.
Open Access
Patients’ perceived benefit and side effects from the use of medicinal cannabis – a cross-sectional survey study from Denmark

2. Dezember 2025

Frederik Rosenbæk, Line Bjørnskov Pedersen, Sonja Wehberg, Jesper Bo Nielsen, Jens Søndergaard

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Objectives Medicinal cannabis (MC) has recently been legalized in a growing number of countries. While MC is considered a potentially safe alternative or add-on to conventional treatments for pain, spasms, neuropathy, and chemotherapy-induced nausea/vomiting, evidence of its effectiveness and safety remains limited. This study aimed to assess patients’ perceived benefits and side effects of MC and explore patterns in side effect experiences. Methods We conducted a Danish nationwide online survey in 2020 among two groups of MC users: one with predefined diagnostic indications (neuropathic pain, chemotherapy-induced nausea/vomiting, or painful spasms from multiple sclerosis/paraplegia) (n=258) and one with other indications (n=786). Perceived benefit and side effects were measured using self-reported responses. We compared perceived benefit to the number of side effects and used a heat plot correlation matrix and exploratory factor analysis to identify patterns. Predicted factor scores were used to compare perceived benefit relative to side effect profiles, stratified by indication group. Results Most patients (67 %) reported a moderate to large effect of MC. Over half experienced side effects, with more than 10 % reporting three or more. Side effects were equally common among patients reporting a moderate to large vs. no to minor effect (p=0.27 and 0.68 for predefined and other indications). Side effects clustered into four groups: cognitive dysfunction, dizziness, xerostomia, and feeling “high.” These were not related to perceived benefit. Conclusions Most patients reported a moderate to large effect from MC. Over one in ten experienced three or more side effects, which were unrelated to perceived treatment effect.
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Assessing the impact of massage and herbal therapies on chronic low back pain: a randomized controlled trial

25. November 2025

Yuwadee Manjit, Pranee Sriraj, Areeya Changthong, Tichanon Promsrisuk, Ranuka Kamolrattanakul, Ratchadawan Aukkanimart

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Objectives Chronic low back pain (cLBP) is prevalent among agricultural workers in Surin Province, Thailand. This study evaluated the efficacy and safety of Thai massage combined with the traditional herbal formula Ya Thamlai Phra Sumeru (YTPS) in reducing pain and improving mobility in individuals with cLBP. Methods A single-blind, randomized controlled trial was conducted with 66 participants assigned to three groups (n=22 each): (1) herbal remedy (Hr) group, receiving 2,000 mg of YTPS twice daily for seven days; (2) Thai massage (Tm) group, receiving massage therapy three times per week; and (3) combined therapy (Tm+Hr) group, receiving both interventions. The active compounds of YTPS were identified by HPLC, and antioxidant capacity was evaluated using DPPH and ABTS assays. Pain and functional outcomes were assessed using the Numerical Rating Scale (NRS), Goniometer (GOM), Flexible Ruler (FR), and Oswestry Disability Index (ODI). Biochemical safety parameters (BUN, creatinine, AST, ALT) and oxidative stress markers (MDA, CAT, GSH, SOD) were analyzed before and after treatment. Results HPLC revealed piperine (19.6 µg) and cannabidiol (5.09 µg) as key active constituents with antioxidant potential. All groups demonstrated improved oxidative profiles, with increased CAT, GSH, and SOD levels and reduced MDA concentrations. The combined therapy group (Tm+Hr) showed the greatest improvements in NRS, GOM, and ODI scores (p<0.05). No significant adverse biochemical changes were observed. Conclusions A seven-day regimen combining Thai massage with YTPS safely and effectively reduced pain and disability while enhancing antioxidant activity. This integrative approach may serve as a practical and culturally relevant therapy for managing chronic low back pain in community healthcare settings.
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Impact of the nitric oxide substrate l-arginine alone and combined with atropine on malathion neuro and hepato-toxicity

28. Oktober 2025

Amany A. Sleem, Eman R. Youness, Nermeen Shaffie, Heba A. Farid, Omar M. E. Abdel-Salam

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Objectives We investigated the impact of the nitric oxide substrate l -arginine on the neuro- and hepato-toxic effects of malathion in rats. Methods Rats were treated intraperitoneally with malathion (150 mg/kg) alone or combined with l -arginine (100, 200 or 400 mg/kg), atropine (2 mg/kg) or l -arginine (200 mg/kg) combined with atropine (2 mg/kg). Rats were euthanized 4 h later, and their brains and livers analyzed for malondialdehyde, nitric oxide (NO), reduced glutathione (GSH), paraoxonase-1 (PON-1). Moreover, butyrylcholinesterase (BChE), interleukin-15 (IL-15) and anti-apoptotic protein B cell/lymphoma-2 (Bcl-2) were determined in brain tissue. Histopatholoy was also performed. Results Malathion significantly raised brain NO and malondialdehyde alongside with a notable drop in PON-1 activity and GSH levels relative to the saline control. Brain BChE and Bcl-2 were markedly inhibited whereas IL-15 significantly increased by malathion. In brain, l -arginine treatment resulted in a significantly increased malondialdehyde, decreased GSH, and increased IL-15. A significant decrease in liver malondialdehyde occurred by l -arginine/atropine or atropine. In contrast, l -arginine, l -arginine/atropine or atropine caused a significant decrease in brain and liver NO levels and increased PON-1 activity. Bcl-2 in brain significantly increased by atropine. Malathion induced brain neuronal and liver degeneration showed marked improvement after atropine alone. Conclusions These results indicated that exogenously administered l -arginine did not protect against the neuro- and hepto-toxic effects of malathion. Meanwhile, the ability of atropine to mitigate the deleterious effects of a toxic dose of malathion provides a strong support to the role of excessive stimulation cholinergic pathways in inflicting such damage.
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Efficacy of traditional medicine in the management of sickle cell disease: a scoping review of current evidence

28. Oktober 2025

Danish Javed, Amit Kumar Rai, Athulya TH, Sai Thejesh Molakapuri, Azeem Ahmad, Gaurav Dhingra

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Introduction While conventional medicine (CM) has improved outcomes for individuals with sickle cell disease (SCD), issues with accessibility, affordability, and potential adverse effects limit its widespread use. As a result, many patients and caregivers turn to traditional medicine (TM) as an alternative approach to managing SCD. This scoping review aims to systematically evaluate the efficacy, safety, and potential mechanisms of action of TM in SCD, while exploring its integration with CM. Content A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, EMBASE, and AYUSH Research Portal. Clinical trials, observational studies, in vitro and in vivo studies, and ethnopharmacological surveys investigating TM interventions in SCD were included. Summary and Outlook Of the 27 selected studies, 11 were in vitro , four in vivo , six clinical trials, and six qualitative surveys. Several medicinal plants demonstrated promising anti-sickling, antioxidant, anti-inflammatory, and immunomodulatory properties. Formulations such as Niprisan ® , Ciklavit ® , and T-AYU-HM™ Premium showed potential in reducing vaso-occlusive crises and improving hematological parameters. However, limitations include variability in herbal formulations, lack of standardization, and inadequate RCTs. While preliminary findings are promising, further well-designed RCTs are needed to establish the efficacy of TM in SCD. Integrating evidence-based TM with CM options could provide a holistic and patient-centered strategy for SCD.
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Pharmacokinetic, toxicological, and antidiabetic evaluation of a novel polyherbal formulation

27. Oktober 2025

Sony Rajan, Ratheesh Mohanan, Svenia P. Jose, Sheethal Sreevallabhan, Sandya Sukumaran, Aditya Ashish

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Objectives The current study aimed to formulate and analyze a novel polyherbal formulation (NPF) comprising of Terminalia arjuna, Centella asiatica and Embelia ribes . Methods NPF was prepared and subjected to preliminary phytochemical screening and FTIR to characterize its bioactive compounds and functional groups. To assess the safety, oral toxicity studies were carried out in Wistar rats. The antidiabetic efficacy was evaluated using the OGTT. Additionally, computational ADME analysis was carried out for the major active molecules – arjunolic acid, embelin, and asiaticoside – to evaluate the pharmacokinetic properties and drug-likeness. Results Presence of various secondary metabolites such as alkaloids, flavonoids, phenolic compounds, saponins, terpenoids, cardiac glycosides, and carbohydrates were confirmed by the phytochemical screening. Key prominent functional groups such as hydroxyl, amine, carbonyl, and alkyne stretching vibrations were detected upon FTIR analysis. Toxicity evaluations indicated no adverse effects, confirming the safety of NPF. Among diabetic rats, groups treated with 200 mg/kg body weight of NPF indicated a significant improvement in glucose tolerance as demonstrated by the OGTT results. ADME profiling showed favorable drug-likeness properties for arjunolic acid and embelin compared to asiaticoside. Conclusions NPF exhibited significant antidiabetic potential and demonstrated safety in animal models.
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Study on a non-pharmacopeial formulation for its hepatoprotective activity against drug induced hepatotoxicity in animal model

17. Oktober 2025

Syeda Asma Firdose, Abdul Wadud

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Objectives This study assessed the hepatoprotective efficacy of a non-pharmacopeial formulation (NPF) against rifampicin-induced hepatotoxicity, aiming to expand the repertoire of hepatoprotective agents in Unani medicine. Methods An acute toxicity study and HPTLC analysis were performed. The experiment utilized 42 Wistar rats, each weighing between 150 and 200 g. The rats were systematically allocated into seven distinct groups, each containing six animals, identified as negative, positive, standard, and test groups A, B, C, and D. Liver damage was induced by oral administration of rifampicin at a dose of 500 mg/kg daily for 30 days, following a 2-hour interval after the administration of standard and test drugs. The standard and test groups received Silymarin (100 mg/kg), NPF, Afsanteen , Kasni , and Asaroon at doses of 167, 117, 167, and 217 mg/kg, respectively, orally once daily for 30 days. Serum levels of marker enzymes (SGOT, SGPT, and ALP), total protein (TP), and albumin (S. Alb) were evaluated. All groups underwent biochemical and histopathological analysis. Results The formulation was deemed safe at a dose of up to 2000 mg/kg. Compared to the standard drug, test groups A and D demonstrated potential protective effects on the liver enzymes. Test groups B and C exhibited normal liver architecture. Conclusions Asaroon (test group D) demonstrated greater efficacy than NPF. Histopathologically, Afsanteen and Kasni were found to be effective. The study indicated that formulations by Unani scholars were more effective than non-pharmacopeial formulations, although the tested NPF remained effective and safe in this study.
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Exploring the neurological pathways of P. ginseng memory-enhancing effects

14. Oktober 2025

Mahdiyeh Hedayati-Moghadam, Fatemeh Seyedi, Hadis Eftekhari, Mohammad Dalfardi, Yousef Baghcheghi

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Panax ginseng , a widely studied herbal remedy, has garnered significant interest for its potential cognitive-enhancing effects, particularly in memory improvement. This narrative review, adhering to the SANRA (Scale for the Assessment of Narrative Review Articles) criteria, collected evidence via a search across PubMed, Scopus, Web of Science, and EMBASE (2000–2023). Key findings suggest that P. ginseng enhances memory through multiple molecular pathways, including modulation of neurotransmitter systems such as acetylcholine, serotonin, dopamine, and glutamate. The herb’s active components, known as ginsenosides, interact with these neurotransmitter systems to regulate synaptic plasticity, neuronal communication, and memory formation processes in the brain. Furthermore, P. ginseng demonstrates antioxidant and anti-inflammatory properties, attenuating oxidative stress and neuroinflammation, which are known contributors to cognitive decline and memory impairment. By reducing neuronal damage and preserving brain health, P. ginseng helps support optimal cognitive function and memory retention. Moreover, P. ginseng influences various signaling pathways involved in memory consolidation and retrieval, including the CREB pathway, BDNF signaling, and the mTOR pathway, through these molecular pathways. P. ginseng promotes neuronal survival, synaptic plasticity, and LTP, ultimately enhancing memory performance. This review underscores the need for standardized methodologies and longitudinal studies to optimize therapeutic applications of P. ginseng in memory-related disorders.
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Experimental evaluation of the Anti-inflammatory and anti-arthritic potential of Saccharum officinarum node extract in FCA-induced arthritic models

15. August 2025

Priyanka Nanasaheb Khamkar, Snehal Ambadas Gojare, Deepti Dinesh Bandawane, Shakuntala Narayan Kawhale

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Background Saccharum officinarum has been traditionally utilized to treat different types of inflammation in ayurvedic medicine. Scientific investigation into the therapeutic potential of plant nodes remains limited and has not been extensively explored. Objectives To investigate the pharmacological efficacy of ethanolic extract of S. officinarum node (EESO) in reducing inflammation and arthritis in experimental models. Methods EESO was obtained via ethanol extraction and analysed for its phytochemical constituents. Rat paw edema was used to check for anti-inflammatory activity by carrageenan induced model, with Methotrexate (1 mg/kg) employed as the conventional reference drug. The EESO node was administered orally to experimental animals at doses of 50, 100, and 200 mg/kg. Measurements of paw thickness were taken at 0, 1, 2, 4, and 6 h. The anti-arthritic activity was assessed in the rat through induction of arthritis using Freund’s complete adjuvant (FCA). Parameters assessed included paw edema, motor coordination, nociceptive threshold, and, post-sacrifice, biochemical (CRP, RF, ALP, AST, ALT), haematological (Hb, RBC, WBC, ESR), cytokine (TNF -α, IL -1, IL -6), radiological, and histopathological markers. Results EESO at 200 mg/kg significantly reduced paw edema by inhibiting inflammatory mediator release and downregulating pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in FCA-induced arthritic rats. Histopathology showed decreased synovial hyperplasia and cartilage erosion due to reduced immune cell infiltration and joint inflammation. These inhibiting inflammatory mediator release, downregulating pro-inflammatory cytokines, reduced immune cell infiltration and joint inflammation scientifically validate the traditional use of EESO in managing arthritis and inflammation. This data sufficiently support the assertion that EESO can be utilized for the treatment of arthritis and inflammation. Conclusions EESO at a dose of 200 mg/kg demonstrated significant anti-inflammatory and anti-arthritic activity in the study, scientifically validating its traditional use. The findings provide adequate preclinical evidence supporting its potential therapeutic role. These results suggest that EESO could serve as a natural treatment option for managing arthritis and inflammation.
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Chronic toxicity and modulatory effects of Deprungsith formulation in Wistar Albino rats

8. August 2025

Yosita Kasemnitichok, Monthaka Teerachaisakul, Tullayakorn Plengsuriyakarn, Kesara Na-Bangchang

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Objectives Psoriasis is a systematic skin disease. Treatment choice is limited due to unsatisfactory clinical efficacy. The study evaluated the safety of Deprungsith formulation following long-term administration (chronic toxicity test) and its potential modulatory effect on hepatic cytochrome P450 (CYP) enzymes in rats. Methods Wistar rats were randomly grouped to receive Deprungsith (125, 500, and 1,000 mg/kg/day) and the satellite (1,000 mg/kg bw) to observe reversibility, as well as distilled water (untreated control) for 9 months. The sentinel-1 group was for environmental risk assessment after 6 months, and the sentinel-2 group was for environmental risk assessment after 9 months). Clinical and behavioral signs, mortality, and histopathology were monitored. Results The chronic toxicity study of Deprungsith revealed no evidence of mortality or serious clinical signs at any dosage level. However, changes in WBC count, serum albumin, and sodium, were observed. Histopathological examination identified mild to moderate liver necrosis and renal interstitial inflammation. Low-dose (125 mg/kg bw) significantly induced CYP1A2 and CYP3A1, while high-dose (1,000 mg/kg bw) inhibited CYP1A2 and CYP3A1 activities. Conclusions Deprungsith formulation was well-tolerated with an MTD (maximum tolerated dose) and NOAEL (no-observed-adverse-effect level) of 1,000 mg/kg bw. Long-term use of Deprungsith formulation in psoriasis patients should be carefully monitored for therapeutic outcomes (side effects from accumulated levels or unsatisfactory efficacy from inadequate CYP1A2 and CYP3A1-mediated metabolism) and potential herb-drug interactions.
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Evaluating the effectiveness of pterostilbene in improving memory and offering neuroprotection in a rat model of Alzheimer’s disease induced by aluminum chloride

31. Juli 2025

Ameer Raheem Waheed, Bahir Abdul Razzaq Mshimesh

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Background and Objectives Alzheimer’s disease (AD) is a neurodegenerative disease and is the predominant etiology of dementia. We hypothesize that the naturally occurring pterostilbene (PTE) at doses of 50 and 100 mg/kg would yield dose-dependent neuroprotective effects, reducing cognitive deficits and pathological hallmarks by modulating biomarkers (Amyloid Beta protein (Aβ), Phosphorylated tau protein (P-tau), Brain-Derived Neurotrophic Factor (BDNF), acetylcholinesterase (ACHE), glutamate (GLU)) and a novel synaptic marker neurogranin (NRGN) in rats induced by aluminum chloride (AlCl 3 ). This current research aims to evaluate the neuroprotective effects of pterostilbene (PTE) against neurobehavioral and pathological alterations induced by aluminum chloride (AlCl 3 ) in rats with Alzheimer’s. Methods 40 rats were divided into five groups, eight in each group. They received 70 mg/kg of body weight AlCl3 intraperitoneally for 30 days, followed by oral administration of PTE at 50 mg/kg or 100 mg/kg, or donepezil at 1 mg/kg for 14 days. The Y-maze and novel object recognition tests were used for the neurobehavioral evaluation of the rats. This was followed by a biochemical evaluation using ELISA kits to demonstrate the impact of PTE on the levels of Aβ, P-tau, BDNF, NRGN, AChE, and GLU. Additional validations were conducted through histopathological evaluation of the cortex and basal ganglia in the rat brain. Using GraphPad Prism 10, statistical data were obtained by ANOVA and Tukey’s multiple comparisons test. The histopathologic score system was determined using the non-parametric Kruskal-Wallis one-way ANOVA k-samples (all pairwise) test. Results PTE at 50 mg/kg significantly increases spontaneous alternation percentage (SAP) by 35.7 % and discrimination index (DI) by 79.7 %, while also considerably lowering Aβ by 70.6 %, P-tau by 33.9 %, BDNF by 59.7 %, NRGN by 40 %, ACHE by 28.8 %, and GLU by 28.4 %. Moreover, PTE at 100 mg/kg significantly increases SAP by 42.9 % and DI by 83.4 %, and substantially decreases Aβ by 83.8 %, P-tau by 45.5 %, BDNF by 69 %, NRGN by 42.5 %, ACHE by 69 %, and GLU by 50.9 % compared to the AlCl3 group. Histopathological evaluation of the cortex and basal ganglia in AlCl3-induced rat brains revealed pathological alterations absent in rats treated with PTE. Conclusions This study supports the hypothesis that PTE can reverse memory loss and pathological markers.
Open Access
Effects of the intravenous application of sodium ascorbate in patients with the diagnosis of sepsis in the intensive care unit – observational, analytical, retrospective, comparative study

17. Juli 2025

Adlay Martinez Ramos, Hugo Mario Galindo Salom, Helber Armando Prieto Lozano, Paulo Andres Lopez Posada, Juan Manuel Martinez, Marixa Guerrero, Carlos Alberto Carrillo Bravo

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Objectives To evaluate whether high-dose intravenous sodium ascorbate improves inflammatory markers in patients with sepsis. Methods A retrospective, observational, analytical, and comparative study was conducted on patients diagnosed with sepsis and admitted to the ICU at Clínica Estrios (Cartagena, Colombia) between July 1 and 30, 2024. Patients receiving standard treatment were compared with those who also received high-dose intravenous sodium ascorbate (>462 mg/kg/day), supplied by Biological Therapies, Australia. The main outcome was the duration of altered SIRS and SOFA scores. Results Patients treated with sodium ascorbate showed a statistically significant reduction in the duration of altered SIRS and SOFA scores ( X 2 =9.00, p=0.003) compared to those who received standard therapy. Conclusions High-dose sodium ascorbate may serve as an effective adjuvant therapy in sepsis.
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The protective effect of hydrolyzed collagen gel from mackerel scad (Decapterus macarellus) to attenuate chronic UVB-induced photodamage

10. Juli 2025

Elisa Herawati, Rizki S. Titisari, Helen Kristin, Filosofia F. T. A. Prasasti, Pipin Agnesia, Okid P. Astirin, Shanti Listyawati, Evi Susanti, Nuniek Herdyastuti, Noer Laily, Fatim Illaningtyas

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Objectives Hydrolyzed collagen (HC) extracted from fish skin is a safe and effective native collagen alternative that can potentially protect skin from experiencing photoaging. This study is among the first to explore HC from mackerel scad ( Decapterus macarellus ) application via in vitro and in vivo approaches. Methods The protective effects of HC were investigated on Mouse Embryonic Fibroblasts (MEFs) induced by acute and chronic UVB, followed by testing of HC gel on UVB-induced photoaging models of mice. Cell viability test using the MTT method was performed on UVB-induced MEFs treated with HC concentrations of 10, 20, 50, and 100 g/mL. A gel form HC was applied topically in UVB-induced skin tissues of animal models and analyzed with ELISA to evaluate the inhibitory effect of MMP-1 and IL-6 expression. Results In vitro analysis showed that HC (10, 20, 50 μg/mL) could increase the viability of acute UVB-induced MEFs at a 60 mJ/cm 2 dose. In chronic UVB exposure, all HC concentrations could protect the viability of induced MEFs at 40 mJ/cm 2 dose. HC gel effectively inhibited the increased expression of MMP-1 and IL-6 in UVB-exposed skin, which may be related to its ability to suppress the activation of MAPK and NF-κB signaling pathways. Furthermore, HC gel intervened in the development of epidermal thickening and dermal layer damage in photoaged skin. Conclusions These findings indicated that HC from mackerel scad skin effectively provided a protective effect against the photoaging process.
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Apitherapy for drug-induced kidney disease: a narrative review on its mechanisms

4. April 2025

Andrés Jagua-Gualdrón, Nicolai Andrés García-Reyes, Holman Leonardo Africano-Lopez

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Objectives The use of medications for the treatment of various diseases often results in kidney damage. Apitherapy is a natural therapeutic tool with potential utility for this purpose. This narrative review analyzes and summarizes the scientific evidence on the use of apitherapy in drug-induced kidney disease. Content This review summarizes and analyzes recent advances in drug-induced kidney disease and explores, based on the available scientific evidence, how apitherapy can modify these mechanisms and be utilized for prevention and treatment. Summary Apitherapy (the complementary and integrative use of beehive products) is a potentially useful therapeutic system for the treatment of various diseases. This review examines the preclinical and clinical evidence available regarding its potential use in drug-induced kidney disease. Outlook Apitherapy has effects on various pathophysiological mechanisms of drug-induced kidney disease, including oxidative stress, inflammation, decreased renal blood flow, glomerular damage, increased membrane permeability, activity of the renin-angiotensin-aldosterone axis, mitochondrial dysfunction, and apoptosis. Further studies in humans are needed to evaluate its efficacy in the clinical setting, but the available evidence is promising.

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CiteScore	3.2	2024, Scopus (Elsevier B.V., 2025)
SCImago Journal Rank	0.321	2024, SJR (Scimago Lab, 2025; Data Source: Scopus)
Source Normalized Impact per Paper	0.583	2024, CWTS Journal Indicators (CWTS B.V., 2025; Data Source: Scopus)

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Editor-in-Chief
Jeremy Y. Ng, PhD, Institute of General Practice and Interprofessional Care, University Hospital Tübingen, Tübingen, Germany; Department of Health Research Methods, Evidence, and Impact, Faculty of Health Sciences, McMaster University, Hamilton, Canada

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Dennis Anheyer, University Hospital Tuebingen, Tuebingen, Germany, dennis.anheyer@uni-tuebingen.de
Kieran Cooley, University of Toronto, Toronto, ON, Canada, kcooley@ccnm.edu
Robert Kam-Ming Ko, Hong Kong University of Science and Technology, Hong Kong, China, bcrko@ust.hk
Zacharias Suntres, Northern Ontario School of Medicine, Thunder Bay, ON, Canada, zacharias.suntres@nosm.ca
Phoebe Zhou, Western Sydney University, Sydney, NSW, Australia, p.zhou@westernsydney.edu.au

Editorial Board

Jon Adams, Distinguished Professor of Public Health and Deputy Head of School, School of Public Health, UTS, Sydney, Australia
Terje Alraek, The National Research Center in Complementary and Alternative Medicine (NAFKAM), Faculty of Medicine at UiT the Arctic University of Norway, Bergen, Norway
John T. Arnason, Department of Biology, University of Ottawa, Ottawa, ON, Canada
Steven K.H. Aung, Associate Clinical Professor, Departments of Medicine and Family, Medicine University of Alberta, AB, Canada
Robert Banner, Department of Anesthesia and Perioperative Medicine, University of Western Ontario, London, ON, Canada
Zhao Xiang Bian, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Heather Boon, Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada
Alieen P. Burford-Mason, DRS Consulting, Toronto, ON, Canada
Harpal S. Buttar, Senior Scientist and Adjunct Professor, Reproduction and Urology Division, Therapeutic Products Directorate, Ottawa, ON, Canada
Dennis Chang, NICM Health Research Institute and Professor of Pharmacology at Western Sydney University, Sydney, NSW, Australia
Alistair Dias, Chemistry Department, University of Toronto, Toronto, ON, Canada
Barbara Findlay, Integrated Health Care Consultant, Richmond, BC, Canada
Gerhard Franz, Faculty of Chemistry and Pharmacy, University of Regensburg, Regensburg, Germany
Daniel F. Gallego-Pérez, Department of Physical Medicine and Rehabilitation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Erik Groessl, Professor of Public Health at UC San Diego and Researcher at VA San Diego, San Diego, CA, USA
Mahabir Gupta, Facultad de Farmacia, Universidad de Panama, Rep. de Panamá
Cory Harris, Department of Biology, University of Ottawa, Ottawa, ON, Canada
Jennifer Hunter, NICM Health Research Institute, Perth, WA, Australia
Connie Kehler, Canadian Herb, Specialty Agriculture and Natural Health Product Coalition, Saskatoon, SK, Canada
Francis C.P. Law, Faculty of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada
Ye-Seul Jennifer Lee, Jaseng Spine and Joint Research Institute, Jaseng Medical Foundation, Seoul, South Korea
Myeong Soo Lee, KM Science Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, South Korea
Brenda Leung, University of Lethbridge, Lethbridge, AB, Canada
C. Leung, Institue Of Chinese Medicine, Chinese University of Hong Kong, Hong Kong, China
Jianping Liu, Professor, Beijing University of Chinese Medicine, Beijing, China
Maria Luz Lara-Marquez, Allergist and Immunologist, Integrative Medicine Specialist, San Diego, CA, USA
Candace Necyk, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada
Siyaram Pandey, Department of Chemistry & Biochemistry, University of Windsor, Windsor, ON, Canada
Michael Smith, National Center for Natural Product Research, University of Mississippi; Oxford, MS, USA; National Centre for Naturopathic Medicine, Southern Cross University, Lismore, NSW, Australia
Amie Steel, Australian Research Consortium in Complementary and Integrative Medicine (ARCCIM), University of Technology, Sidney, Ultimo, NSW, Australia
Jerome Yager, Research Integrative Health Institute, University of Alberta, Edmonton, AB, Canada
Linda Zhong, Biomedical Sciences and Chinese Medicine, School of Biological Sciences at Nanyang Technological University in Singapore, Singapore

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Farida Akhter, ON, Canada
Managing.Editor.JCIM@degruyter.com

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Heike.Jahnke@degruyterbrill.com

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1553-3840

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2194-6329

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Erstveröffentlichung:

1. Januar 2004

eISSN: 1553-3840

ISSN: 2194-6329

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