Herb-Drug Interactions in Neurological Disorders: A Critical Appraisal.

BACKGROUND: Herbal drugs are being used worldwide in a variety of debilitating neurological and psychiatric disorders such as cerebrovascular accident, Alzheimer's disease, Parkinson's disease and schizophrenia. However, unlike drugs of modern medicine, herbal drugs are complex products containing multiple pharmacologically active constituents. The nature and relative amounts of these constituents vary due to diverse factors such as but not limited to source of the plant(s), local environmental conditions, parts of the plant used, storage, method of extract preparation, accidental contamination or intentional adulteration. Further, they are handled by the human body like modern drugs and subjected to the processes of absorption, distribution, metabolism and excretion. In each of these processes, they can potentially interact with modern drugs due to sharing of similar transport proteins, metabolizing cytochrome P450 (CYP450) enzymes and uptake / efflux pumps. Moreover, herbal drugs can also inhibit or induce CYP450 enzymes or inactivate transporters leading to Herb-Drug interactions (HDIs). METHOD: In this narrative review, we have analyzed the clinically reported as well as potential HDIs between 10 common herbal drugs viz. Ginkgo, Ginseng, St. John's Wort, Grapefruit, Black and Long Pepper, Curcumin, Brahmi, Kava, Garlic and Valerian and modern medicines used in neurological and psychiatric disorders with their proven or postulated underlying mechanism(s). RESULTS: Though a number of potential pharmacokinetic and/or pharmacodynamic HDIs have been examined, clinically significant alteration of response to modern medicines and/or serious adverse effects are apparently scarce except for Grapefruit and St. John's Wort. CONCLUSION: Physicians and patients should exercise caution when using herbal drugs and modern medicines concomitantly so that the recognized serious HDIs can be avoided.

Clinical efficacy of water extract of stem bark of Terminalia arjuna (Roxb. ex DC.) Wight & Arn. in patients of chronic heart failure: a double-blind, randomized controlled trial.

BACKGROUND: The stem bark of Terminalia arjuna (Roxb. ex DC.) Wight and Arn. (Arjuna) is used in Indian system of medicine (Ayurveda) for treatment of various cardiac diseases, including heart failure. However, well designed clinical trials exploring its efficacy and safety in chronic heart failure (CHF) are lacking. PURPOSE: To ascertain the add-on efficacy and safety of a standardized water extract of stem bark of Arjuna (Arjuna extract) in CHF patients on standard pharmacotherapy. STUDY DESIGN: Double-blind, parallel, randomized, placebo-controlled add-on clinical trial. METHODS: After approval of institutional ethics committee, 100 patients of CHF of New York Heart Association (NYHA) functional class II on standard pharmacotherapy having an echocardiographic left ventricular ejection fraction (LVEF) ≤ 40% were consecutively recruited with informed consent and randomized 1:1 to Arjuna extract 750 mg or matching placebo twice daily. The primary outcome measure was change in LVEF at 12 weeks. Secondary outcome measures included changes in (i) NYHA functional class, (ii) distance covered in 6 min walk test (6MWT), (iii) quality of life (QoL), as determined by the Kansas City Cardiomyopathy Questionnaire (KCCQ), (iv) plasma brain natriuretic peptide, (v) plasma cytokines (interleukin-6, high sensitivity C-reactive protein and tumour necrosis factor-α) and (vi) oxidative stress markers [serum thiobarbituric acid reactive substances (TBARS), red blood cell (RBC) superoxide dismutase (SOD), RBC catalase and RBC glutathione (GSH)] at 6 and 12 weeks. Safety assessment was done by adverse event monitoring and laboratory investigations. Results were expressed as mean ± SD or median (interquartile range) and analysed with intention-to- treat principle using appropriate two-sided statistical tests. A p-value < 0.05 was considered significant. RESULTS: Arjuna extract was well-tolerated, but did not change LVEF (24.3 ± 7.1 versus 25.5 ± 7.7%; p = 0.4) or secondary outcome measures except preservation of RBC catalase activity [1275(104, 10350) versus 1243.5(104, 10350) U/g haemoglobin; p = 0.01] compared to placebo. Significantly greater percentage increases occurred in distance covered in 6 MWT, RBC-SOD, RBC catalase, RBC GSH and in symptom severity and stability domains of KCCQ in patients on Arjuna extract versus those on placebo, on a post-hoc analysis, between subgroups of patients who improved in these outcomes. CONCLUSION: Arjuna extract did not improve LVEF in CHF patients over 12 weeks, although there was improvement in functional capacity, antioxidant reserves and symptom-related QoL domains in some patients.