Regar Raj Kumar, Sharma Mahima, Behera Sangita, Gupta Pankaj, Lal Roshan, Prajapati Suneel, Kumar Arun, Kumar Godlaveti Vijay Narasimha, Saka Vara Prasad, Agrawal Anurag, Verma Digvijay, Kaushik Subhash
Department of Pharmacology, Drug Standardization, Dr. D.P. Rastogi, Central Council for Research in Homoeopathy (DDPR-CRIH), Noida 201301, Uttar Pradesh, India.
Department of Pharmacology, Drug Standardization, Dr. D.P. Rastogi, Central Council for Research in Homoeopathy (DDPR-CRIH), Noida 201301, Uttar Pradesh, India.
Fitoterapia. 2025 Jul;184:106649. doi: 10.1016/j.fitote.2025.106649. Epub 2025 May 28.
Candidiasis, a superficial or systemic infection affecting skin, mucous membranes, and internal organs, is increasingly challenging to treat due to drug-resistant Candida albicans strains. Natural products such as Terminalia chebula (TC) have shown promising in vitro antifungal activity, yet their in vivo efficacy and mechanism of action remain underexplored. Here, homoeopathic formulations of TC were evaluated through a sequential in vitro, in vivo, and in silico approach. In vitro, TC-M exhibited a high total phenolic content (56.5 mg GAE/mL) and potent antioxidant activity (DPPH 32.5 mg GAE/mL; ABTS 26.7 mg GAE/mL). Broth microdilution assays determined a minimum inhibitory volume of 20 μL (∼0.55 mg/mL) against C. albicans. In vivo, systemic candidiasis was induced in cyclophosphamide-immunosuppressed rats. TC-M, 6C, and 30C significantly improved 8-day survival (62.5-75 % vs. 12.5 % in disease controls), normalized leukocyte counts and antioxidant enzyme activities (SOD, catalase, GSH), and reduced renal fungal burden and histopathological damage. Phytochemical profiling by LC-MS/MS identified 33 major bioactive constituents in TC-M, including phenolic acids, flavonoids, tannins, and terpenoids. In silico, key phytochemicals were docked against fungal targets: β-tubulin, DHFR, and sterol 14α-demethylase. Both chebulic and ellagic acids replicated griseofulvin's critical interactions with β-tubulin, gallic acid, chebulic acid-targeted DHFR, and chebulic acid-bound sterol 14α-demethylase. This is the first integrated evaluation of TC homoeopathic formulations using in vitro, in vivo, and in silico approaches, revealing its significant antifungal, antioxidant, and immunomodulatory activities against systemic candidiasis. Clinical validation is warranted.
念珠菌病是一种影响皮肤、粘膜和内脏器官的浅表或全身感染，由于耐药白色念珠菌菌株的出现，其治疗难度越来越大。诸如诃子（Terminalia chebula，TC）等天然产物已显示出有前景的体外抗真菌活性，但其体内疗效和作用机制仍未得到充分研究。在此，通过体外、体内和计算机模拟的连续方法对诃子的顺势疗法制剂进行了评估。在体外，TC-M表现出高总酚含量（56.5 mg GAE/mL）和强大的抗氧化活性（DPPH 32.5 mg GAE/mL；ABTS 26.7 mg GAE/mL）。肉汤微量稀释试验确定对白色念珠菌的最小抑菌体积为20μL（约0.55 mg/mL）。在体内，在环磷酰胺免疫抑制的大鼠中诱导全身性念珠菌病。TC-M、6C和30C显著提高了8天生存率（62.5%-75%，而疾病对照组为12.5%），使白细胞计数和抗氧化酶活性（超氧化物歧化酶、过氧化氢酶、谷胱甘肽）正常化，并减轻了肾脏真菌负荷和组织病理学损伤。通过LC-MS/MS进行的植物化学分析确定了TC-M中的33种主要生物活性成分，包括酚酸、黄酮类、单宁和萜类化合物。在计算机模拟中，关键植物化学物质与真菌靶点（β-微管蛋白、二氢叶酸还原酶和甾醇14α-脱甲基酶）进行对接。诃子酸和鞣花酸都复制了灰黄霉素与β-微管蛋白、没食子酸、靶向诃子酸的二氢叶酸还原酶以及与诃子酸结合的甾醇14α-脱甲基酶的关键相互作用。这是首次使用体外、体内和计算机模拟方法对诃子顺势疗法制剂进行综合评估，揭示了其对全身性念珠菌病具有显著的抗真菌、抗氧化和免疫调节活性。有必要进行临床验证。
