title: Evaluation of herb-drug interaction of a polyherbal Ayurvedic formulation through high throughput cytochrome P450 enzyme inhibition assay.
abstract: BACKGROUND
  Arishtas are Ayurvedic formulation made with decoction of herbs. Arjunarishta formulation is being used in Ayurveda for cardio-protective activity. Ashwagandharishta formulation possesses antioxidant, anti-atherosclerotic and anti-stress properties. Ridayarishta, a novel empirical formulation was prepared using combination of selected ingredients from these two formulations to support healthy heart functions and to reduce stress.
  
  
  OBJECTIVE
  Aim of the Study was to investigate herb-drug interaction (HDI) of Ridayarishta formulation through human hepatic cytochrome P450 (CYP450) enzyme inhibition assay.
  
  
  METHODS
  Ridayarishta formulation was phyto-chemically standardized against arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A using high performance thin layer chromatography (HPTLC) analysis. The formulation was standardized with respect to ethanol by gas chromatographic (GC) analysis. HDI was evaluated with Ridayarishta formulation and amlodipine besilate, atenolol, atorvastatin, metformin, glipizide glimepiride cocktail using high throughput CYP450 enzyme inhibition assay; against CYP1A2, 2C19, 2D6 and 3A4 isozymes.
  
  
  RESULTS
  Contents of arjunolic acid, arjunetin, berberine, piperine, resveratrol and withaferin-A in Ridayarishta formulation were found to be 1.76±0.12, 1.51±0.09, 1.85±0.05, 3.2±0.12, 1.21±0.08, and 2.16±0.09ppm, respectively. Quantity of ethanol in Ridayarishta was found to be 7.95±0.023% (V/V). Ridayarishta showed significantly higher (P<0.001) IC50value against CYP1A2 (IC50-13.80±1.96µg/mL), 2C19 (IC50-14.343±2.28µg/mL), 2D6 (IC50-0.897±0.28µg/mL) and 3A4 (IC50-32.057±2.51µg/mL) compared to positive controls such as furafylline, tranylcypromine, quinidine and ketoconazole respectively. Cocktail of herbal formulation and cardio protective, antihypertensive, anti-diabetic drugs showed significantly (P<0.001and P<0.01) less or negligible HDI.
  
  
  CONCLUSIONS
  Ridayarishta formulation alone and cocktail with amlodipine besilate, atenolol, atorvastatin, metformin, glipizide, glimepiride had negligible or insignificant effect on CYP450 inhibition. It may be concluded that consumption of Ridayarishta along with selective cardio protective, antihypertensive and anti-diabetic conventional medicine is safe with negligible or without any significant CYP450 (CYP1A2, 2C19, 2D6 and 3A4) inhibition mediated HDI.
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India. Electronic address: subratapandit@gmail.com.
authors.forename: Subrata
authors.initials: S
authors.lastname: Pandit
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Satyajyoti
authors.initials: S
authors.lastname: Kanjilal
authors.affiliation: Althea Life Sciences Limited, 3, Factory Road, Adj. Safdarjung Hospital Ring Road, New Delhi 110029, India.
authors.forename: Anshumali
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: Althea Life Sciences Limited, 3, Factory Road, Adj. Safdarjung Hospital Ring Road, New Delhi 110029, India.
authors.forename: Anika
authors.initials: A
authors.lastname: Chaudhary
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Dipankar
authors.initials: D
authors.lastname: Banerjee
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: B N
authors.initials: BN
authors.lastname: Bhatt
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Avinash
authors.initials: A
authors.lastname: Narwaria
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Singh
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Kakoli
authors.initials: K
authors.lastname: Dutta
authors.affiliation: Althea Life Sciences Limited, 3, Factory Road, Adj. Safdarjung Hospital Ring Road, New Delhi 110029, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Jaggi
authors.affiliation: Althea Life Sciences Limited, 3, Factory Road, Adj. Safdarjung Hospital Ring Road, New Delhi 110029, India.
authors.forename: Anu T
authors.initials: AT
authors.lastname: Singh
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Research & Development center, Healthcare Division, Emami Limited 13, BT Road, Kolkata 700056, India.
authors.forename: Chandra Kant
authors.initials: CK
authors.lastname: Katiyar
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D001599:Berberine / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D041743:Herb-Drug Interactions / Q000502:physiology*; D006801:Humans; D008515:Medicine, Ayurvedic; D008862:Microsomes, Liver / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D010936:Plant Extracts / Q000378:metabolism* / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D000077185:Resveratrol; D012503:Saponins / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology; D054358:Withanolides / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D004364:Pharmaceutical Preparations; D010880:Piperidines; D010936:Plant Extracts; D053284:Polyunsaturated Alkamides; D012503:Saponins; D013267:Stilbenes; D014315:Triterpenes; D054358:Withanolides; D001599:Berberine; C484967:arjunetin; C061640:arjunolic acid; D003577:Cytochrome P-450 Enzyme System; C009684:withaferin A; D000077185:Resveratrol; C008922:piperine
keywords: Ayurveda; Cytochrome P450 inhibition; Herb-drug interaction; Human liver microsomes; Ridayarishta formulation; Standardization