Amity Institute of Virology and Immunology, Amity University Uttar Pradesh, Sec-125, Noida, Uttar Pradesh, India.
Dabur Research Foundation, 22, Site IV, Sahibabad, Ghaziabad, Uttar Pradesh, India.
J Ethnopharmacol. 2024 Nov 15;334:118596. doi: 10.1016/j.jep.2024.118596. Epub 2024 Jul 18.
Psoriasis, a widespread skin condition impacting over 100 million individuals globally, is characterised by uncontrolled hyperproliferation of keratinocytes, abnormal apoptosis, and excessive secretion of inflammatory cytokines and angiogenic factors. Traditional use of Alstonia scholaris (L.) R.Br., Wrightia tinctoria (Roxb.) R.Br. and Solanum xanthocarpum Schrad. & Wendl. in Ayurveda and Siddha medicinal systems have shown promising anti-inflammatory and wound-healing properties. However, underlying mechanisms of their phytoactivity in addressing psoriasis-like skin inflammation on human keratinocytes remain largely unexplored.
The study was aimed to investigate anti-psoriatic potential of ethyl acetate and ethanolic extracts of A. scholaris, W. tinctoria and S. xanthocarpum in human keratinocyte cell line (HaCaT).
Ethyl acetate and ethanolic extracts of A. scholaris (ASEA and ASE), W. tinctoria (WTEA and WTE) and S. xanthocarpum (SXEA and SXE) were first subjected to phytochemical screening through high-performance liquid chromatography (HPLC) using their marker compound loganin, kaempferol and chlorogenic acid, respectively. The proliferation inhibition efficiency of these extracts was measured using MTT assay on HaCaT cell line. Subsequently, the apoptotic effect of these extracts on HaCaT cell line was determined by JC-1 and Annexin V assays. Furthermore, IL-8 and RANTES levels were measured in TNF-alpha-induced HaCaT cell line post-treatment with these extracts to determine their anti-inflammatory properties.
ASEA, ASE, WTEA, WTE, SXEA and SXE significantly inhibited proliferation of keratinocytes (HaCaT cells) and resulted in the induction of apoptotic markers (mitochondrial membrane potential and phosphatidyl serine externalization). Additionally, pro-inflammatory markers (IL-8 and RANTES levels) were downregulated in HaCaT cells. The anti-proliferative effects were particularly distinct at higher concentrations (200 μg/mL), with inhibition rates reaching over 85% for W. tinctoria and S. xanthocarpum extracts. In apoptotic assays, notable increases in late apoptotic or necrotic cell populations and significant losses in mitochondrial membrane potential were observed. All extracts markedly reduced the secretion of inflammatory mediators IL-8 and RANTES.
All three plants exerted an anti-psoriatic effect at the cellular level via multiple parameters (anti-proliferative, pro-apoptotic, anti-inflammatory effect). This study provides insight into the mechanism of action of ASEA, ASE, WTEA, WTE, SXEA and SXE and highlights their promising potential for development as herbal therapeutic agents for psoriasis. It emphasizes the need for further pharmacological evaluation and toxicological studies of these extracts.
银屑病是一种全球性的广泛皮肤疾病，影响全球超过 1 亿人。其特征是角质细胞的不受控制的过度增殖、异常凋亡以及炎症细胞因子和血管生成因子的过度分泌。在阿育吠陀和悉达医学体系中，阿尔斯通学者氏树（L.）R.Br.、莱特氏扭肚藤（Roxb.）R.Br.和茄属植物黄果（Schrad. & Wend.）的传统用途具有有希望的抗炎和伤口愈合特性。然而，其在人类角质细胞上针对银屑病样皮肤炎症的植物活性的潜在机制在很大程度上仍未得到探索。
本研究旨在研究乙酸乙酯和乙醇提取物对人角质细胞系（HaCaT）的阿尔斯通学者氏树（ASEA 和 ASE）、莱特氏扭肚藤（WTEA 和 WTE）和茄属植物黄果（SXEA 和 SXE）的抗银屑病潜力。
首先，通过高效液相色谱法（HPLC）使用其标记化合物马钱苷、山奈酚和绿原酸对 ASEA 和 ASE、WTEA 和 WTE、SXEA 和 SXE 的乙酸乙酯和乙醇提取物进行植物化学筛选。然后，通过 MTT 测定法测量这些提取物对 HaCaT 细胞系的增殖抑制效率。随后，通过 JC-1 和 Annexin V 测定法确定这些提取物对 HaCaT 细胞系的凋亡作用。此外，在 TNF-α诱导的 HaCaT 细胞系中，用这些提取物处理后，测量白细胞介素-8 和 RANTES 水平，以确定其抗炎特性。
ASEA、ASE、WTEA、WTE、SXEA 和 SXE 显著抑制角质细胞（HaCaT 细胞）的增殖，并导致诱导凋亡标志物（线粒体膜电位和磷脂酰丝氨酸外化）。此外，HaCaT 细胞中的促炎标志物（IL-8 和 RANTES 水平）下调。在较高浓度（200μg/mL）时，抗增殖作用特别明显，W. tinctoria 和 S. xanthocarpum 提取物的抑制率超过 85%。在凋亡测定中，观察到晚期凋亡或坏死细胞群体显着增加，并且线粒体膜电位显着降低。所有提取物均显着减少了炎症介质 IL-8 和 RANTES 的分泌。
三种植物均通过多种参数（抗增殖、促凋亡、抗炎作用）在细胞水平上发挥抗银屑病作用。本研究深入了解 ASEA、ASE、WTEA、WTE、SXEA 和 SXE 的作用机制，并强调它们作为银屑病草药治疗剂的潜在开发前景。它强调了对这些提取物进行进一步药理学评估和毒理学研究的必要性。
