Volume 31, Issue 1

Mitragyna speciosa , commonly known as Ketum or Biak in Malaysia and Kratom in Thailand, is a native plant to Southeast Asia and has various pharmacological benefits. Mitragynine (MG) is the principal alkaloid found in the leaves of Mitragyna speciosa and has been reported to be responsible for the plant’s therapeutic actions. Traditionally, local communities use Kratom preparations for relief from different types of pain. The potential analgesic effects of MG using rodent models have been reported in literatures. We have reviewed the published analgesic and pharmacokinetic studies and all of these findings showed the routes of drug administration, doses employed, and type of vehicles used to solubilize the drug, varied considerably; hence this posted difficulties in predicting the drug’s pharmacokinetic-response relationship. A rational approach is warranted for accurate prediction of dose-response relationship; as this is essential for the development of MG as an alternative medicinal drug for pain management. PKPD modeling would serve as a better method to understand the dose-response relationship in future MG preclinical and clinical studies.

Background Heat shock proteins (HSPs) are a class of highly conserved proteins responsible for various functions critical to cell survival. Pharmacological induction of HSPs has been implicated in the regulation of neuronal loss and functional deficits in peripheral and central nervous system injuries. Accordingly, the present study was conducted to investigate the effect of trehalose on spinal expression of HSP27 , HSP70 and caspase-3 genes following traumatic spinal cord injury (SCI) in rats. Methods Male rats weighing 250–300 g underwent laminectomy and were divided into four groups including sham, SCI (received SCI), vehicle (received SCI and phosphate buffer saline intrathecally) and trehalose (received 10 mM trehalose intrathecally following SCI). On days 1, 3 and 7 after injury, HSP27 , HSP70 and caspase-3 genes transcripts were quantified in spinal cord tissues via a real-time PCR technique. In addition, locomotor function was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. Results SCI induced the expression of HSP27 , HSP70 and caspase-3 genes and BBB score at all time points. Trehalose treatment upregulated HSP27 , HSP70 genes expression at 1 day after SCI. Interestingly, a significant reduction in the expression of HSP27 and HSP70 genes was observed on days 3 and 7 following trauma compared with the vehicle group (p < 0.01). Caspase-3 gene showed a decrease in expression in the trehalose-treated group at all times. In addition, neurological function revealed an improvement after treatment with trehalose. Conclusion This study suggests that the neuroprotective effect of trehalose is mediated via regulation of HSP27 and HSP70 , which are involved in cytoprotection and functional recovery following SCI.

Background : Utilization of Morinda lucida for the treatment of ailments such as malaria, diarrhea, infertility in women, and dysentery in many countries including Nigeria is on increase due to its efficiency, availability, and affordability. However, its cytogenotoxicity has not been elucidated. This study investigated the phytochemical constituents and possible genotoxic and cytotoxic effects of M. lucida leaf extract in Swiss albino male mice using bone marrow micronucleus and sperm morphology assays. Methods : Plant materials was collected, thoroughly washed, and air-dried at room temperature prior to maceration. The extract was assessed for the presence of the phytochemical compounds. Swiss albino male mice ( Mus musculus ) (n=4) were treated with different concentrations of this extract (400 mg/kg, 800 mg/kg, and 1200 mg/kg) while distilled water was used as negative control. Results : Phytochemical analysis revealed that the extract contains saponins, terpenoids, flavonoids, glycosides, and tannins. We observed micronucleated polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) of 3.20%, 1.10%, and 1.95% at different concentrations of 400 mg/kg, 800 mg/kg, and 1200 mg/kg respectively in the treated animals. The result showed no significant increase in the frequency of abnormalities (p < 0.05) when compared to the negative control; however, in separate analysis of mono-micronucleated PCE and mono-micronucleated NCE per group, a significant increase at 400 mg/kg and 1200 mg/kg concentrations was observed. The sperm anomalies decreased with increase in concentration. Conclusions : This study recommends 800 mg/kg concentration of the plant extract; however, it should be further and properly investigated as it contains some pharmaceutical components that can be used for pharmacological purposes.

Background Naturally ripened fruits play a vital role in human nutrition. Under certain conditions, synthetic chemicals like calcium carbide (CaC 2 ) and ethylene glycol (EG) are being freely used illegally in India and other countries for fruit ripening without serious concern on its toxic effects. This preclinical study evaluated the toxicity on different organs after the exposure of industrial-grade CaC 2 and EG to the rats. Methods Acute toxicity was induced by the oral administration of a single dose of chemicals to the rats, and their morbidity and mortality were monitored. For subacute study, different organs of animals were analyzed biochemically and histologically after the exposure of low doses of chemicals for 30 days. Results At an acute dose of 5 mg/kg body weight of CaC 2 , 85% of the animals were found dead within 14 days; however, no mortality was observed following EG administration. At subacute doses, RBC and hemoglobin levels were found to be declined (p < 0.01), whereas total WBC and platelet counts, especially lymphocytes, were elevated remarkably (p < 0.01). Total protein, albumin, and urea were also found to be increased (p < 0.01). Histopathological observations support the toxicity in rats at higher doses of CaC 2 and EG. Conclusions The study revealed that the artificial fruit-ripening agents like CaC 2 and EG cause toxic effects on the internal organs of rats. The subsequent inflammatory response might have weakened the immune system. This in turn suggests the requisite for urgent measures to regulate the use of harmful synthetic agents in fruit ripening.

Background Averrhoa carambola fruit is consumed by many people because of its sweetness and medicinal values. However, there is a dearth of researched information on its complete toxicity profile. This study investigated the possible toxicity potentials of star fruit juice in female albino rats. Methods Thirty-five rats assigned into seven groups of five rats each and administered with varying doses (0, 250, 500, 1000, 2000, 4000 and 5000 mg/kg) of the juice were used for acute toxicity studies. Another 20 rats assigned to four groups (A–D) of five rats each were administered the juice at 0, 600, 400 and 200 mg/kg body weight orally for 28 days. On the 29th day, whole blood, sera and vital organs were collected for hematological, serum biochemical and histopathological analyses, respectively. Results Acute study results indicate that the juice was safe even at 5000 mg/kg after 48 h. In the subacute studies, there were no significant (p < 0.05) differences in all hematological parameters, total protein, albumin and globulin values of the treated groups compared with those of the control group. The aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities, as well as urea, creatinine and malondialdehyde values of the rats treated with the juice were significantly (p < 0.05) higher than those of the control rats in a dose-dependent manner. The liver and kidney histomorphologies of the rats treated with the juice showed lesions of degeneration and necrosis when compared with those of the control. Conclusion The juice of A. carambola is both nephrotoxic and hepatotoxic but had no deleterious effects on the hematology.

Background Chlorpyrifos (CPF) is an organophosphate insecticide, acaricide, and miticide used primarily to control foliage and soilborne insect pests on a variety of food and feed crops. Since trace amounts of these compounds are found in water and food products, they easily enter into the organ system unnoticed. In the same way, the compound or its metabolite gets transmitted from the parent to the embryo mainly through blood vessels. Since blood vessels form the major route of transport, it is pertinent to study the effect of these compounds during angiogenesis. The effect of CPF and 3,5,6-trichloro-2-pyridinol (TCPy) on the angiogenesis of chick embryo was evaluated in the chorioallantoic membrane (CAM) using an ex vivo model. Methods Nine-day-old incubated eggs where inoculated with various doses of CPF and TCPy. After 48 h of incubation, the CAM layers were retrieved and analyzed using angiogenesis software to obtain the density of blood vessels. Histomorphometric studies were performed to measure the thickness of vessel walls. The expression of VEGF, VEGFR2, and N-cadherin genes responsible for angiogenesis were analyzed. Results The exposure to the parent compound CPF and its metabolite TCPy promoted angiogenesis in groups administered with lower concentration of the pesticide and its metabolite, whereas a decline in angiogenesis was observed at higher concentrations. These observations were made by analyzing the density, histomorphometry results, and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) results. The density, thickness, and lumen size of blood vessels in the groups with low concentration of CPF and TCPy were 28.34, 9 μm, and 30 μm, respectively, whereas in the groups with higher CPF and TCPy concentrations, they were 12, 3 μm, and 9 μm, respectively. Conclusions Hence, CPF and its metabolites interfere with angiogenesis in the CAM of chick embryos. Because of their estrogen-mimicking ability, pesticides are the prime etiological suspects of increasing alteration in blood vessel formation. These results may be of help in future studies on the effect of CPF in embryonic growth, wound healing, diabetes, and tumors.

Background Antihypertensive medications are one among the most highly used drugs across the globe as well as in India, and their prescribing pattern will be erratic despite the various clinical guidelines. Few studies address the pattern and adherence to the standard treatment guidelines in India. This study aimed to review the prescribing pattern of antihypertensive medications in a rural tertiary care teaching Indian hospital and to investigate the adherence to the Joint National Commission-8 (JNC-8) guidelines on prevention, detection, evaluation, and treatment of hypertension in adults. Methods A prospective observational study was conducted among the participants from four different inpatient wards who are aged >18 years, without gender restriction. The prescription pattern was reviewed and adherence to the JNC-8 guidelines was also assessed. A purposive sampling technique was adopted and descriptive statistics were used in Statistical Package for the Social Sciences v16. Results Of the 101 participants included in the study, 62 (61.39%) were female, 23.76% were aged <30 and >60 years, and the other 52.48% belong to the range of 30–60 years. As per JNC-8 guidelines, 4.95%, 17.82%, 44.55%, and 32.67% of patients were classified as normal, pre-hypertensive, stage I, and stage II, respectively. Most of them (31.68%) were free from comorbidities. The most (23.76%) prescribed drug was calcium channel blocker (CCB), and 15.84% of the patients received combination therapy. Treatment was effective in 70.30% of the patients through analyzing their blood pressure even though the adherence to the JNC-8 guidelines was only in 54.46%. Conclusions Our study revealed that CCB was the most prescribed drug, and in spite of the only 50% adherence rate, treatment was effective in the majority of the population. The treatment outcome can be improved if the adherence rate is increased further.

Background The Global Status Report 2017 reveals that 11% of Indians indulge in binge drinking. Chronic alcohol intake may lead to cardiac problems and hypertension. The aim of this study was to evaluate cardiovascular risk among asymptomatic chronic alcoholics. Methods A total of 80 asymptomatic chronic alcoholics of South Indian origin, from the psychiatry ward of Sri Ramachandra Institute of Higher Education and Research, India were diagnosed with alcohol dependence syndrome(ADS). Group I includes alcoholics for 10 years or less and group II includes alcoholics for more than 10 years. Alcohol consumption was measured using the DSM IV criteria. Blood pressure (BP) and electrocardiographic (ECG) data were measured on admission and 2 weeks later. The paired t-test compared a significant outcome of the two sets of data at p ≤ 0.05 level of significance. Results Forty percent of the patients were found to be hypertensive and only 2.5% were found to be pre-hypertensive on admission. The mean age of the hypertensives was 46.9 and nonhypertensives was 42.1 The difference in the BP evaluated after 2 weeks was staggering – systolic BP had a mean fall of 6.1 mm Hg (p < 0.001) and diastolic BP 2.25 mm Hg (p = 0.001). The electrocardiogram results showed significant changes like left ventricular hypertrophy, abnormal T waves, and QT prolongation. Conclusions Chronic alcoholism is a major criterion for heart abnormalities such as elevated BP and left ventricular enlargement, and our study supports this as we see that alcohol consumption for more than 10 years shows significant deterioration. Further clinical observations and long-term prospective studies are needed to confirm these observations.

Background Since their discovery in the early 1960s, doxorubicin (DOX) remains the most effective anticancer drug. However, this drug has confirmed to be a double-edged sword because it causes a cardiomyopathy that leads to congestive heart failure. Ghrelin, a multi-functional peptide, plays an important role in cardiovascular protection. Therefore, we investigated the effects of ghrelin on vascular endothelial growth factor-beta (VEGF-B) and connexin-43 (Cx43) expression in DOX-induced cardiomyopathy. Methods Forty adult male rats were divided randomly into four groups: normal, normal + ghrelin, DOX-induced cardiomyopathy, and DOX-induced cardiomyopathy + ghrelin. Biochemical and histopathological analysis, electrocardiograph (ECG), heart rate, systolic blood pressure (SBP), and immunohistochemical staining of VEGF-B and Cx43 were assessed for all rats in heart tissue specimens. The duration of the study was 2 weeks. Results DOX-induced cardiomyopathy in rats showed significant ECG changes such as prolongation of PR, QT, QTC intervals and ST segment, a decrease in amplitude and an increase in the duration of QRS complex, bradycardia, and a decrease in SBP. Also, rats in the DOX group showed myocardial histopathological damage in the form of severe fibrosis with decreased expression of Cx43 and a non-significant difference in expression of VEGF-B when compared to normal rats. Treatment with ghrelin resulted in a significant improvement in all the studied parameters and was associated with an increase in VEGF-B and Cx43 expression. Conclusions Ghrelin has a beneficial effect against DOX-induced cardiomyopathy which may be mediated through VEGF-B and Cx43 expression in the myocardium. Ghrelin is a promising cardioprotective drug in DOX-induced cardiomyopathy patients, but further studies are needed to evaluate its use.

Background This study evaluates the antioxidant activity and enzyme inhibitory properties of the n -butanol fraction of Senna podocarpa leaves on α-amylase, α-glucosidase, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), tyrosinase, arginase, phosphodiesterase 5 (PDE-5), and angiotensin converting enzyme (ACE). Methods The total phenol and flavonoids, iron (Fe) chelation, and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging were used to determine the antioxidant activity, and the inhibitory activities of α-glucosidase, α-amylase, AChE, BChE, tyrosinase, arginase, PDE-5 and ACE were also assessed. Results The n -butanol fraction of S. podocarpa shows high total phenol and total flavonoid contents. The n -butanol fraction of S. podocarpa leaves also chelates Fe 2+ and ABTS radicals. The n -butanol fraction of S. podocarpa leaves also inhibited α-glucosidase, α-amylase, AChE, BChE, tyrosinase, arginase, PDE-5, and ACE at the concentration tested. Chromatographic analysis displayed the presence of β-elemene, phytol and caryophyllene oxide chrysophanol, 3-oxo-methyl ester, α-humulene, β-caryophyllene, rhein, emodin, and α-copaene. Conclusions Hence, the n -butanol fraction of S. podocarpa leaves demonstrates encouraging feat in controlling and/or managing cognitive dysfunction such as Alzheimer’s disease and also hypertension, diabetes, erectile dysfunction, endothelial dysfunction, and hyperpigmentation.

Background Gongronema latifolium Benth. (family Apocynaceae ) leaves ( GL ) has interesting medicinal properties. The effects of extracts from G. latifolium on blood pressure (BP) and the possible mechanisms of action were also investigated. Methods The ultrahigh resolution liquid chromatography orbitrap MS analysis was used to identify the phytochemicals present. Normotensive Wistar rats were anesthetized with sodium pentobarbitone (40 mg/kg) intraperitoneally, and the jugular vein was cannulated for infusion of drugs while the carotid artery was cannulated for direct BP measurement. GL extract (5–20 mg) alone or with nifedipine (10 mg/kg), atropine (2 mg/kg), L-NAME (5 mg/kg), methyl blue (3 mg/kg) and propranolol (1 mg/kg) were administered intravenously to Wistar rats and direct BP measurements were carried out. Results Systolic and diastolic BP levels (128/90 mm Hg; MAP 103 ± 3 mm Hg) and heart rates were all significantly (p < 0.01) decreased after GL administration. Raised mean arterial pressure (MAP) and heart rate by atropine, L-NAME and methyl blue were significantly (p < 0.01) reduced after GL administration, while propranolol significantly (p < 0.01) inhibited hypotension caused by GL. Infusion of GL reduced MAP (95 ± 3 mm Hg) comparable with nifedipine (93 ± 2 mm Hg), a calcium channel blocker. The phytochemicals identified were 34 compounds, including oleanolic acid derivatives, flavonoids, antioxidant fatty acids, 2 coumarins and 2 iridoids. Conclusions These results suggest that G. latifolium has hypotensive properties mediated by the synergistic activity of the compounds, probably via the β-adrenergic blockade mechanism.

Background Anxiety is a common ailment of high co-morbidity with epilepsy, a chronic neurologic disease characterized by recurrent seizures. Current drugs used for these conditions have several limitations such as disabling side effects, relapse, and ineffectiveness in certain population necessitating the search for alternative options. The aqueous leaf extract of Cymbopogon citratus (CYC) is widely used for its various health-promoting effects including relief of seizures and anxiety in ethnomedicine. This present study describes its effects on convulsions, anxiety-like behaviors, and social interaction in mice. Methods Male Swiss mice were pretreated orally with CYC (25, 50, and 100 mg/kg), diazepam (1 mg/kg), or distilled water (10 mL/kg) 60 min before induction of convulsions with intraperitoneal (i.p.) injection of picrotoxin (10 mg/kg), pentylenetetrazole (PTZ; 85 mg/kg), or isoniazid (300 mg/kg). The animals were then observed for the occurrence of seizure for 30 min or 2 h for isoniazid. The effects of CYC on anxiety-like behaviors, social interaction, and spontaneous motor activity (SMA) were evaluated in naive mice. Results CYC (25–100 mg/kg) did not prevent convulsions nor delay the latency to convulsions induced by picrotoxin, PTZ, or isoniazid. Pretreatment with CYC (50 and 100 mg/kg, p.o) produced anxiolytic-like effect, decreased SMA, and also enhanced social interaction behavior in naive mice. Conclusions The results of this study suggest that CYC did not exhibit an anticonvulsant property in mice injected with picrotoxin, PTZ, or isoniazid, but its anxiolytic-like activity and social interaction-promoting effect might be of benefit as an adjuvant in improving the quality of life of epileptic patients.

Background Commelina benghalensis Linn. (Family: Commelinaceae) is a common weed available in Bangladesh with several uses in traditional medicine. However, the chemical profile of this medicinal plant is scarce in relation to its medicinal uses. The aerial parts of this plant have been investigated for the isolation of secondary metabolites and evaluation of the biological activities. Methods Major phytochemical groups were analyzed using chromogenic reagents, whereas n -hexane soluble fractionates of the methanol extract were subjected to 1 H nuclear magnetic resonance (NMR) spectroscopic analysis. The antioxidant property of the obtained compounds was evaluated using 1,1-diphenyl-2-picryl-hydrazyl (DPPH). Results Dammara-12-en-3-one (CB-1), stigmasterol (CB-2) and 3 (2,3,4,5,6-pentahydroxy)-cinnamoyl dammara-12-ene (CB-3) were isolated from the n -hexane fractionate of methanol extract of C. benghalensis . In the study of DPPH radical scavenging activity, IC 50 values were predicted to be 790.18, 4186.94 and 2001.16 μg/mL for CB-1, CB-2 and CB-3, respectively, whereas standard ascorbic acid showed IC 50 at 1.26 μg/mL. Conclusions Two new dammarane-type triterpene (CB-1 and CB-3) and one phytosterol (CB-2) were identified in C. benghalensis with mild antioxidant property.

Background Youth population has a common tendency to use androgenic steroids. The reasons for such abuse vary from performance enhancement to muscle building in order to enhance physical appearance. Such rampant abuse, aided by fitness centers and gym trainers, has a huge risk of side effects such as hepatic dysfunctions and increased risk of infections. Case presentation We report a case of 21-year-old man who started with anabolic steroids, namely testosterone enanthate, nandrolone decanoate and boldenone undecylenate injections, for the purpose of muscle building and strength training at his fitness center. He presented to his family physician after 2 months with upper neck swelling on right side 5 × 4 cm for 15–20 days. He was started on Augmentin 625 mg tablet three times a day for 7 days. On seventh day, swelling persisted, and fine needle aspiration cytology (FNAC) was performed, which was suggestive of granulomatous lesion likely to be tuberculosis. The patient was started with anti-tubercular therapy (ATT) under category A, but swelling did not improve and repeated FNAC was advised. The ATT was withheld and Augmentin tablet was restarted for another 3 days. A revised diagnosis of acute suppurative lymphadenitis was made, and an incision and drainage of the abscess was performed. The patient was started on Amikacin 500 intramuscular injection for 5 days along with faropenem and cefuroxime axetil tablets for 14 days. He initially started recovering but returned with pustular discharge from the incision mark. It was decided to reinitiate the ATT-intensive phase medication for another 2 months. The patient finally recovered with complete healing of the wound. The frequent change of treating physician and misuse of antimicrobials made the diagnosis tougher, contributing to delay in the optimum therapy. Conclusion This case highlights the abuse of multiple steroids together in the form of stacking by a young adult, which leads to a rare serious adverse effect such as suspected tubercular reactivation.