Volume 12, Issue 1 -

Glucocorticoids (GC) are universally accepted agents for the treatment of anti-inflammatory and immunosuppressive disorders. They are used in the treatment of rheumatic diseases and various inflammatory diseases such as allergy, asthma and sepsis. They bind with GC receptor (GR) and form GC–GR complex with the receptor and exert their actions. On activation the GC–GR complex up-regulates the expression of nucleus anti-inflammatory proteins called as transactivation and down-regulates the expression of cytoplasmic pro-inflammatory proteins called as transrepression. It has been observed that transactivation mechanisms are notorious for side effects and transrepressive mechanisms are identified for beneficial anti-inflammatory effects of GC therapy. GC hampers the function of numerous inflammatory mediators such as cytokines, chemokines, adhesion molecules, arachidonic acid metabolites, release of platelet-activating factor (PAF), inflammatory peptides and enzyme modulation involved in the process of inflammation. The GC resistance is a serious therapeutic problem and limits the therapeutic response of GC in chronic inflammatory patients. It has been observed that the GC resistance can be attributed to cellular microenvironment changes, as a consequence of chronic inflammation. Various other factors responsible for resistance have been identified, including alterations in both GR-dependent and GR-independent signaling pathways of cytokine action, hypoxia, oxidative stress, allergen exposure and serum-derived factors. The present review enumerates various aspects of inflammation such as use of GC for treatment of inflammation and its mechanism of action. Molecular mechanisms of anti-inflammatory action of GC and GC resistance, alternative anti-inflammatory treatments and new strategy for reversing the GC resistance have also been discussed.

Background : Stephania abyssinica (Dillon & A. Rich) Walp (Menispermaceae) is a medicinal plant used in the west region of Cameroon to treat arterial hypertension. The present study evaluated the vasorelaxant effects of the aqueous (AESA) and methanol (MESA) extracts from the fresh leaves of S. abyssinica on aorta rings isolated from Wistar rats. Methods : Aorta rings with intact endothelium were contracted with KCl (60 mM) or phenylephrine (10 −5 M) and exposed to cumulative concentrations of each extract, ranging from 10 to 1,000 µg/mL. The vasorelaxant effects of AESA were further evaluated in presence of N ω -nitro-L-arginine methyl ester ( L -NAME, 10 −4 M), tetraethylammonium (TEA, 5 µM), glibenclamide (5 µM), propranolol (5 µM), and the association glibenclamide–propranolol (AGP). In another set of experiments, the effect of AESA was evaluated on calcium-induced contraction in a hyperpotassic milieu. Results : AESA and MESA exhibited a concentration-dependent vasorelaxation on KCl-contracted aortic rings with respective EC 50 of 160.10 and 346.50 µg/mL. AESA similarly relaxed aortic rings contracted with phenylephrine (EC 50 , 176.80 µg/mL). The vasorelaxant activity of AESA was not significantly affected by L -NAME but was markedly reduced by TEA, glibenclamide, propranolol, and AGP. AESA strongly inhibited the Ca 2+ -induced contraction by 95%. Conclusions : These results support the use of S. abyssinica against arterial hypertension and suggest that the vasorelaxant effect of AESA is not mediated via the endothelium/nitric oxide pathway. AESA relaxant properties might be due to an inhibition of Ca 2+ influx and/or the activation of ATP-sensitive K + channels probably via the stimulation of β-adrenergic receptors.

Background : Chromolena odorata is a tropical species of flowering shrub in the family Asteraceae, leaves of it have been reported to be widely used as herbal remedy for the treatment of various ailments. It is particularly reported to be useful in the healing of wounds. Methods : We investigated the possibility of amelioration of intestinal ischemia–reperfusion (IR) injury in rats treated with methanolic extract of C. odorata (MECO). Wistar albino rats were divided randomly into five groups of six animals each as control, IR-treated, IR+200 mg/kg MECO, IR+400 mg/kg MECO, and IR+200 mg/kg vitamin C. Pre-treatment with MECO or vitamin C was for 7 days. Results : The contents of hydrogen peroxide (H 2 O 2 ) and malondialdehyde (MDA) were significantly reduced by MECO and vitamin C, while there were significant enhancements of the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), as well as the content of reduced glutathione (GSH) in pre-treated rats compared to IR-treated rats. Glutathione S-transferase (GST) activity was not significantly affected in all the groups. Histopathological examination of small intestinal mucosa revealed significant attenuation of intestinal pathology in animals pre-treated with MECO, while IR injury produced severe villi erosion, necrosis, and inflammatory cell infiltrations. Conclusions : The present study highlights the antioxidant activities of MECO and its ability to inhibit inflammatory cell infiltration as mechanisms involved in its protection against IR injury in the intestine of rats, an effect that was largely comparable to that of vitamin C.

Background : The effects of Orchis anatolica plant roots on adult male mice testicular structure and function were explored and compared with those of the red Korean Panax ginseng . Methods : Both plants were administered orally to two separate mice groups at a dose of 800 mg/kg/day for 35 days and compared with control group. After treatment, 5 mice of each group were sacrificed and total mice weights, reproductive organs’ weights, spermatogenesis, and androgenic serum markers were investigated. The remaining mice from all groups were allowed to mate with virgin female mice to explore male fertility potential. Results : Results indicated that body and organs’ weights were increased significantly in mice treated with Orchis anatolica where only slight changes were observed in red Korean Panax ginseng treated and control mice. Intestinal testicular Leydig cells and germinal cells counts were elevated significantly in mice treated with Orchis anatolica plant when compared with the other two groups. Testicular dynamics parameters recorded in both testes and caudae epididymides were found to be increased only in Orchis anatolica treated mice. Although testosterone serum titer was observed to be elevated in both treated mice groups a marked elevation was observed only in Orchis anatolica treated mice. Follicular stimulating hormone blood serum titer was also elevated obtained in Orchis anatolica treated mice when compared with the other two groups. The fertility index of male mice treated with Orchis anatolica plant was enhanced to a greater value when allowed mating with virgin female mice if compared with male mice fertility index recorded in the other two groups. Conclusions : We can conclude that Orchis anatolica plant could be more useful to improve testicular functions and structural parameters in mice when compared with red Korean Panax ginseng .

Background : Although some studies in the southeast part of Guizhou Province have suggested that Miaoyao Fanggan Sachets (MFS) prevent influenza, little is known about its influence on immune systems. Influenza virus mainly infects immune-compromised individuals. The effects of MFS have mainly been recognized in clinical practice. However, there have been relatively few studies on its biological mechanism. Here we investigated whether MFS was able to affect the mucosal immunization and the activation of alveolar macrophages (AM), CD4+and CD8+ T-cells in vivo . Methods : Eighty Kunming male mice were treated with MFS continuously or intermittently with Yu-Ping-Feng powder (YPF-P) (positive control group) or with normal saline (NS) (control group) for 4 weeks, respectively. Mice treated with MFS were further divided into the continuous inhalation group (12 h daily/4 weeks) and the discontinuous inhalation group (1 h, three times a day for 4 weeks). Mice in both groups were placed under 0.5 m 3 masks which had four ventilation holes (10×15 cm) containing 40 g MFS. Positive control mice were orally treated with YPF-P 0.2 mg/10 g/day once a day for 4 weeks. Control mice were orally treated with equal volumes of NS once a day for 4 weeks. MFS was replaced every 6 days. Administration of YPF-P was used as a positive control since it has been used as an established Traditional Chinese Medicine (TCM) treatment before. After 4 weeks, mice in all experimental groups were sacrificed. IgA and IgG1 in lung and blood serum were detected by Western blot and enzyme-linked immuno sorbent assay (ELISA). The expression of alveolar macrophages (AM) in mice was analyzed by immunochemistry test based on CD68+staining. Blood samples were collected in which CD4+and CD8+T-cells were analyzed by flow cytometry. Results : Mice continuously and intermittently inhaling MFS showed a moderate increase in IgA and IgG1 protein levels compared with mice in the control groups. There was also a slightly significant increase in the number of AM in the continuous inhalation group compared with mice in the control groups (p<0.05). Furthermore, compared with controls, there was also a slightly significant increase in the number and percentage of CD4+and CD8+T-cells in both the continuous inhalation group and the discontinuous inhalation group (p<0.05). Conclusions : MFS was able to up-regulate the protein levels of sIgA and IgG1. Meanwhile, MFS could activate AM, CD4+and CD8+T-cells in mice. Our data have, for the first time, demonstrated that the protection against influenza by MFS is partly through activation of the innate and adaptive cell-mediated immune responses, indicating MFS as a potential new immune-modulatory agent for respiratory tract infectious disease.

Background : Acalypha wilkesiana (Euphorbiaceae) is highly accepted for traditional treatment of human plasmodiasis in Africa. Methods : The toxicological effects of the aqueous leaf extract of A. wilkesiana were studied in 45 male and female Wistar albino rats. An acute toxicity testing was done using 21 rats divided into seven groups and LD50 determined. In the sub-chronic toxicity study, the extract was administered orally over a period of 28 days to rats in three groups with doses of 400 mg kg−1, 800 mg kg−1 and 1,600 mg kg−1, respectively, and the fourth group administered with water served as control. Blood samples were collected for hematological and serum biochemical analysis; organs of the animals were harvested for histopathological examination. Results : The acute toxicity testing showed that the extract was non-toxic at doses up to 3,000 mg kg −1 and the LD50 was calculated to be 2,828.34 mg kg −1 . The study showed that at 1,600 mg kg −1 dose, the extract caused a decrease in the level of neutrophils (NEUT) while lymphocytes (LYMP) were statistically significantly increased. The administration of the extract also resulted in varying significant dose dependent increase in the levels of aspartate amino transferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). There were also significant increases in the level of total protein (TP), urea (URN) and albumin (GLB) especially at 1,600 mg kg −1 dosage. Histopathology showed that the extract caused mild to severe significant lesions that are dose dependent in the liver and kidney when compared with the control group. Conclusions : Prolonged administration of high dose of A. wilkesiana extract has tendency to cause organ toxicity.

Background : Anorexia is a common symptom for patients with advanced cancer. Gentian, ginger, and turmeric have traditionally been used to stimulate appetite. We tested these agents in combination, in a pilot study to assess tolerability in patients indicating 4/10 or worse anorexia on the Edmonton Symptom Assessment System, and who were not currently on chemotherapy. We collected exploratory data on the patient’s appetite using a visual analogue scale. Methods : Between 2009 and 2012, 17 patients were enrolled in arm 1 (turmeric 1 g and ginger 1 g orally twice daily, and gentiana lutea tincture 1 mL three times a day, for 14 days). The three patients enrolled in arm 2 received the same doses of ginger and turmeric but no gentian. All patients completed a daily appetite diary and a weekly symptom assessment. Results : In arm 1, seven patients (41%) completed treatment. Seven patients (41%) stopped early because of unacceptable toxicity or patient-initiated discontinuation, and 3 stopped because of other reasons. All patients in arm 2 stopped taking the study medication within few days of starting the treatment, leading the study committee to recommend stopping the trial. The most common adverse effects attributed to study drugs were nausea (6 patients), vomiting (3), fatigue (3), diarrhea (2) and bloating (2). There was no statistically significant effect seen on appetite. Conclusions : At the doses used in this study, the combination of ginger, turmeric, and gentian is not tolerated well in cancer patients. Future studies should use fewer agents or lower doses.

Background : The aim of this study was to investigate and evaluate the efficacy of Rheum emodi in the management of primary dysmenorrhoea. Methods : A randomized, single-blind, standard controlled trial compared efficacy of R. emodi against mefenamic acid on diagnosed subjects of primary dysmenorrhoea for three consecutive cycles. Experimental group (n=30) received capsules of R. emodi powder two times a day, two days before the expected date of menstruation, and continued first three days of menstruation, while control group (n=15) participants received mefenamic acid capsules three times a day on the same protocol. The primary outcome measures were reduced in severity and duration of pain, assessed by visual analogue scale (VAS) and verbal multidimensional scoring system (VMSS), and secondary outcome measures were overall improvement of dysmenorrhoea and improved in quality of life (QOL). Statistical analysis was done by repeated measures analysis of variance and Chi-square/Fisher Exact test. Results : The menstrual pain was significantly decreased in both groups after three-cycle intervention. Significant changes were observed in VAS (p<0.001) and VMSS (p<0.001) in the experimental group. There is a significant (p<0.001) reduction in duration of pain in both the groups. Associated symptoms and QOL were markedly improved after treatment (p<0.001). Conclusions : It has been clear from the above result that R. emodi is an effective herb in alleviating symptoms of primary dysmenorrhoea. It can serve as an alternative treatment without any apparent side effects. These results deserve further investigations.

Background : The purpose of this paper was to assess the perceptions and attitudes of modern medical practitioners (MMPs) and traditional medical practitioners (TMPs) about traditional medical practice and to analyze the utilization of traditional medicine in Eritrea. Methods : The data for this study were collected in a 10-month period from January to October 2004. A cross-sectional study was conducted in three sub-zones of Eritrea: Dekemhare , Ghinda , and Maekel . A total of 500 (250 each) MMPs and TMPs, and 1657 households were included in the study. Data were collected both by questionnaire and an interview (with key informants). Results : Our study reveals that there is a significant difference in perception and attitude between MMPs and TMPs about traditional medical practice in Eritrea. Their differences lie not only in their way of thinking but also in their perceptions of man and health. Our study further shows that in most rural communities in Eritrea, the use of traditional medicine and self-care is extensive. This is the case even in the presence of the supposedly free/subsidized health care available in government health centers. Conclusions : Higher confidence in traditional medicine for the treatment of serious illnesses, irrespective of availability of western medical service in many parts of Eritrea, indicates the need for selective integration of traditional medical practice with the primary healthcare system of the country.

Background : Patients suffering from intractable diseases and individuals seeking relief from mild symptoms resort to treatments outside the modern medical paradigm, such as complementary and alternative medicine (CAM). In order to improve doctor–patient communication about CAM, it is essential to evaluate CAM usage among social groups likely to choose it in the future. Therefore, we aimed to evaluate how university students – individuals highly subject to future CAM usage – perceive CAM and the factors affecting their choice of CAM use. Methods : We conducted a questionnaire survey with 1,096 Japanese university students not studying medical subjects. Results : The term CAM was known to 11% of the subjects. Modalities they most associated with CAM were art therapy (353 subjects), hot spring therapy (349), and aromatherapy (345). They had experience taking vitamins, trace elements, other supplements (498), and nutritional drinks (483). Several subjects wanted to experience shiatsu massage (373) and hot spring therapy (303). Multiple regression analysis of the modalities that the subjects wanted to experience revealed a 42% multiple coefficient of determination for prioritizing modalities that the subject associated with CAM, showing a large contribution of this deciding factor. Conclusions : Although most subjects were not familiar with the term CAM, many of them had decided to ingest substances in the CAM category on the basis of self-judgment and without adequate knowledge. Because such behavior can be detrimental to health, medical professionals should be aware of CAM usage among their patients and seek effective communication with them in order to enable safe CAM practice.

Background : This study aims to further elucidate the demographic and diabetes characteristics of diabetic patients in Australia who use complementary and alternative medicines (CAM). Methods : This was a prospective, cross-sectional questionnaire-based study of 149 patients with diabetes attending a general endocrine clinic in a tertiary referral hospital in Sydney, Australia. Results : Thirty-seven patients (25%) stated they had used CAM therapies within the past 5 years. Vitamins (53%) were the most common CAM therapy used. A greater number of CAM nonusers reported calf pain whilst walking (21% vs. 9%, p =0.051), and HbA 1c values were lower for CAM nonusers (7.7% vs. 8.1%, p =0.057). Amongst CAM users, a majority of patients (85%) did not consult with their specialist or general practitioner prior to starting CAM therapy. Conclusions : With the increasing burden of diabetes, health practitioners will need to be more vigilant and understanding of the potential impact of CAM use on diabetes management.

The following are abstracts of oral and poster research presentations given at the 2014 IN-CAM Research Symposium, The Next Wave of Complementary and Integrative Medicine and Health Care Research, held November 6 to 8, 2014 at the Marriott Hotel, Calgary Alberta, Canada. The abstracts are grouped under the distinct groups and activities, which took place during the Symposium. For more information, please visit: www.incamresearch.ca.