Bhowmik Rudranil, Shaharyar Md Adil, Kanakal Mahibub Mahamadsa, Sarkar Arnab, Farhana Syeda Ayesha, Hussain Shalam M, Khan Abdullah, Mandal Pallab, Roshan S, Mitra Achintya, Karmakar Sanmoy
Bioequivalence Study Centre, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, 700032, India.
Faculty of Pharmacy, Quest International University, Ipoh, Perak, Malaysia.
Heliyon. 2024 May 28;10(11):e31937. doi: 10.1016/j.heliyon.2024.e31937. eCollection 2024 Jun 15.
This study aims to pharmacologically validate Haridra Khanda (HK) and Manjishthadi Kwatham (brihat) (MMK) in allergy management using and studies to rationalize the prescription of these two ayurvedic polyherbal drug formulations, which are currently used in Indian government hospitals. Experimental animals received HK and MMK orally from day 0 to day 14 and histamine (1 mg/kg b.w/i.v) and 1 % evans blue (EB) (0.1 mL) via tail vein on day 14. The compound 48/80 (intracutaneous) challenged mice model followed the same technique. The former mimicked acute anaphylaxis and the latter mast cell degranulation. For both models, EB dye leakage was quantified spectrophotometrically to determine vascular permeability. Plasma histamine was measured in Compound 48/80-induced animals using LC-ESI-MS/MS. The guineapig received HK and MMK p.o. and 0.6 % histamine sprayed in a histamine chamber to simulate allergic rhinitis. Blood eosinophil count and sneeze rate were measured in histamine-challenged guineapigs. Goat R.B.C. membrane stability assay (mammalian cell membrane toxicity) and intracellular histamine-induced cytosolic Ca release assay in Chinese hamster ovary (CHO) cells were performed . For both histamine and Compound 48/80 challenged animals, HK (22.81 % and 14.58 %) and MMK (19.71 % and 22.40 %) significantly reduced EB dye leakage (p < 0.05). Both formulations, HK and MMK considerably (p < 0.05) decreased plasma histamine (29.62 % and 25.37 % respectively) in mice and eosinophilic count (11.56 % and 9.94 % respectively) and sneeze rate (42.58 % and 29.03 % respectively) in guinea pigs. In membrane stability experiment, HK and MMK reduced RBC lysis. Both HK and MMK raw/dialysate blocked CHO cell cytosolic Ca release. HK and MMK activities mimic mast cell stabilization with possible H1 receptor inactivation seen by decreased Ca efflux and thus indicate potential for allergic rhinitis management. The combination of activities is usually related with curative and prophylactic therapy and might lead future clinical trials and therapies.
本研究旨在通过体内和体外研究从药理学角度验证哈里德拉干达(HK)和曼吉什塔迪夸塔姆(布里哈特)(MMK)在过敏管理中的作用,以合理化这两种阿育吠陀多草药药物制剂的处方,它们目前在印度政府医院中使用。实验动物从第0天到第14天口服HK和MMK,并在第14天通过尾静脉注射组胺(1毫克/千克体重/静脉注射)和1%伊文思蓝(EB)(0.1毫升)。化合物48/80(皮内注射)激发的小鼠模型采用相同技术。前者模拟急性过敏反应,后者模拟肥大细胞脱颗粒。对于这两种模型,通过分光光度法定量EB染料渗漏以确定血管通透性。使用液相色谱-电喷雾串联质谱法(LC-ESI-MS/MS)测量化合物48/80诱导的动物血浆中的组胺。豚鼠口服HK和MMK,并在组胺室中喷洒0.6%组胺以模拟过敏性鼻炎。测量组胺激发的豚鼠的血液嗜酸性粒细胞计数和喷嚏率。进行山羊红细胞膜稳定性试验(哺乳动物细胞膜毒性)和中国仓鼠卵巢(CHO)细胞中细胞内组胺诱导的胞质钙释放试验。对于组胺和化合物48/80激发的动物,HK(22.81%和14.58%)和MMK(19.71%和22.40%)均显著降低EB染料渗漏(p<0.05)。HK和MMK两种制剂均显著(p<0.05)降低小鼠血浆组胺(分别为29.62%和25.37%)以及豚鼠嗜酸性粒细胞计数(分别为11.56%和9.94%)和喷嚏率(分别为42.58%和29.03%)。在膜稳定性实验中,HK和MMK减少了红细胞裂解。HK和MMK的原液/透析液均阻断了CHO细胞的胞质钙释放。HK和MMK的活性模拟了肥大细胞稳定作用,可能通过减少钙外流导致H1受体失活,因此表明其在过敏性鼻炎管理方面具有潜力。这些活性的组合通常与治疗和预防疗法相关,可能会引领未来的临床试验和治疗。