Mohsin Syeda Aroosa, Shaukat Shazia, Nawaz Marya, Ur-Rehman Tofeeq, Irshad Nadeem, Majid Muhammad, Hassan Syed Shams Ul, Bungau Simona, Fatima Humaira
Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
Department of Pathology, Shifa College of Medicine, Islamabad, Pakistan.
Front Pharmacol. 2022 Nov 24;13:1067697. doi: 10.3389/fphar.2022.1067697. eCollection 2022.
This study aims at the biological profiling of , , , , , , , and as alternatives against onychomycosis to combat the treatment challenges. An extract library of aqueous (DW), ethyl acetate (EA), and methanol (M) extracts was subjected to phytochemical and antioxidant colorimetric assays to gauge the ameliorating role of extracts against oxidative stress. RP-HPLC quantified therapeutically significant polyphenols. Antifungal potential (disc diffusion and broth dilution) against filamentous (dermatophytes and non-dermatophytes) and non-filamentous fungi (; ), synergistic interactions (checkerboard method) with terbinafine and amphotericin-B against resistant clinical isolates of dermatophytes ( and ) and non-dermatophytes ( spp., , and ) time-kill kinetics, and protein estimation (Bradford method) were performed to evaluate the potential of extracts against onychomycosis. The highest total phenolic and flavonoid content along with noteworthy antioxidant capacity, reducing power, and a substantial radical scavenging activity was recorded for the extracts of . Significant polyphenolics quantified by RP-HPLC included rutin (35.71 ± 0.23 µg/mgE), gallic acid (50.17 ± 0.22 µg/mgE), catechin (93.04 ± 0.43 µg/mgE), syringic acid (55.63 ± 0.35 µg/mgE), emodin (246.32 ± 0.44 µg/mgE), luteolin (78.43 ± 0.18 µg/mgE), myricetin (29.44 ± 0.13 µg/mgE), and quercetin (97.45 ± 0.22 µg/mgE). Extracts presented prominent antifungal activity against dermatophytes and non-dermatophytes (MIC-31.25 μg/ml). The checkerboard method showed synergism with 4- and 8-fold reductions in the MICs of , , , , and extracts and doses of amphotericin-B (Amp-B) and terbinafine (against non-dermatophytes and dermatophytes, respectively). Furthermore, the synergistic therapy showed a time-dependent decrease in fungal growth even after 9 and 12 h of treatment. The inhibition of fungal proteins was also observed to be higher with the treatment of synergistic combinations than with the extracts alone, along with the cell membrane damage caused by terbinafine and amp-B, thus making the resistant fungi incapable of subsisting. The extracts of , , , , and have proven to be promising alternatives to combat oxidative stress, resistance, and other treatment challenges of onychomycosis.
本研究旨在对[具体植物名称1]、[具体植物名称2]、[具体植物名称3]、[具体植物名称4]、[具体植物名称5]、[具体植物名称6]、[具体植物名称7]和[具体植物名称8]进行生物学特征分析,作为治疗甲癣的替代药物,以应对治疗挑战。对水提取物(DW)、乙酸乙酯提取物(EA)和甲醇提取物(M)的提取物库进行了植物化学和抗氧化比色法测定,以评估提取物对氧化应激的改善作用。反相高效液相色谱(RP-HPLC)对具有治疗意义的多酚进行了定量。针对丝状真菌(皮肤癣菌和非皮肤癣菌)和非丝状真菌([具体真菌名称1];[具体真菌名称2])进行了抗真菌潜力(纸片扩散法和肉汤稀释法)测试,采用棋盘法研究了提取物与特比萘芬和两性霉素B对皮肤癣菌([具体皮肤癣菌1]和[具体皮肤癣菌2])和非皮肤癣菌([具体非皮肤癣菌属]、[具体真菌名称3]和[具体真菌名称4])耐药临床分离株的协同相互作用,进行了时间杀菌动力学研究,并采用考马斯亮蓝法进行蛋白质定量分析,以评估提取物治疗甲癣的潜力。[具体植物名称9]提取物的总酚和黄酮含量最高,同时具有显著的抗氧化能力、还原能力和较强的自由基清除活性。RP-HPLC定量分析的重要多酚类物质包括芦丁(35.71±0.23μg/mgE)、没食子酸(50.17±0.22μg/mgE)、儿茶素(93.04±0.43μg/mgE)、丁香酸(55.63±0.35μg/mgE)、大黄素(246.32±0.44μg/mgE)、木犀草素(78.43±0.18μg/mgE)、杨梅素(29.44±0.13μg/mgE)和槲皮素(97.45±0.22μg/mgE)。提取物对皮肤癣菌和非皮肤癣菌表现出显著的抗真菌活性(最低抑菌浓度-MIC为31.25μg/ml)。棋盘法显示[具体植物名称10]、[具体植物名称11]、[具体植物名称12]、[具体植物名称13]和[具体植物名称14]提取物与两性霉素B(Amp-B)和特比萘芬(分别针对非皮肤癣菌和皮肤癣菌)的剂量协同作用,使MIC分别降低4倍和8倍。此外,协同治疗即使在治疗9小时和12小时后也显示出真菌生长随时间的减少。与单独使用提取物相比,协同组合治疗对真菌蛋白质的抑制作用也更高,同时特比萘芬和两性霉素B导致细胞膜损伤,从而使耐药真菌无法存活。[具体植物名称15]、[具体植物名称16]、[具体植物名称17]、[具体植物名称18]和[具体植物名称19]提取物已被证明是应对氧化应激、耐药性和甲癣其他治疗挑战的有前景的替代药物。
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