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具有不同甾醇内酯组成的两种印度人参提取物治疗活性和毛囊诱导的药物靶点鉴定及相关分子机制研究

Study of Drug Target Identification and Associated Molecular Mechanisms for the Therapeutic Activity and Hair Follicle Induction of Two Ashwagandha Extracts Having Differential Withanolide Constitutions.

作者信息

Cavaleri Franco, Chattopadhyay Sukalpa, Palsule Vrushalee, Kar Pradip Kumar, Chatterjee Ritam

机构信息

Biologic Pharmamedical Research, 688-2397 King George Blvd, White Rock V4A 7E9, BC, Canada.

Cooch Behar Panchanan Barma University, Panchanan Nagar, Vivekananda Street, Cooch Behar 736101, West Bengal, India.

出版信息

J Nutr Metab. 2023 Sep 30;2023:9599744. doi: 10.1155/2023/9599744. eCollection 2023.

DOI:10.1155/2023/9599744
PMID:37808919
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10560109/
Abstract

BACKGROUND

Ashwagandha extracts play a significant role in traditional Indian medicine to help treat a wide range of disorders from amnesia, erectile dysfunction, neurodegenerative and cardiovascular diseases, cancer, stress, anxiety, and many more. Ashwagandha root is enriched with bioactive plant metabolites of which withanolides are the most important ones. The concentration and constitution of withanolides primarily determine ashwagandha's potency and pharmacology. Various factors modulate the withanolide constitution in the plant-derived extracts, rendering inconsistent therapeutic efficacy. Standardisation of the extraction protocol and a better understanding of the pharmacology mechanism of different extracts with varied withanolide constitutions is therefore critical for developing reliable, repeatable, and effective ashwagandha-based treatment.

OBJECTIVES

Here, we work toward defining indication mechanisms for two varieties of ashwagandha extract-ASHWITH (ASH-Ext1) and Regenolide (ASH-Ext2)-with different proprietary withanolide proportions.

METHODS

ASH-Ext1 was studied for antioxidant signaling modulation using HEK293, HeLa, and A549 cells, and ASH-Ext2 was studied for subcellular drug targets associated with the reactivation and longevity of human hair follicles, using primary human hair follicle dermal papilla cells (HFDPCs).

RESULTS

Study findings support the antioxidant activity and Nrf2 signaling modulation by ASH-Ext1 in various cell models. Of note, ASH-Ext2 was found to increase -catenin and telomerase reverse transcriptase (TERT) protein expression levels in HFDPCs.

CONCLUSION

The results of drug target modulation show us that the withanolide constitution associated with different extraction protocols influences the pharmacological potential of the extract significantly and points to the value of standardisation not only of total withanolide content but also of internal withanolide proportions.

摘要

背景

印度人参提取物在传统印度医学中发挥着重要作用,有助于治疗多种疾病,包括失忆、勃起功能障碍、神经退行性疾病和心血管疾病、癌症、压力、焦虑等等。印度人参根富含生物活性植物代谢产物,其中内酯是最重要的成分。内酯的浓度和组成主要决定了印度人参的效力和药理作用。各种因素会调节植物提取物中内酯的组成,导致治疗效果不一致。因此,标准化提取方案并更好地理解不同内酯组成的提取物的药理机制,对于开发可靠、可重复且有效的基于印度人参的治疗方法至关重要。

目的

在此,我们致力于确定两种不同专利内酯比例的印度人参提取物——ASHWITH(ASH-Ext1)和Regenolide(ASH-Ext2)的适应症机制。

方法

使用HEK293、HeLa和A549细胞研究ASH-Ext1对抗氧化信号的调节作用,使用原代人毛囊真皮乳头细胞(HFDPCs)研究ASH-Ext2与人类毛囊重新激活和寿命相关的亚细胞药物靶点。

结果

研究结果支持ASH-Ext1在各种细胞模型中的抗氧化活性和Nrf2信号调节作用。值得注意的是,发现ASH-Ext2可增加HFDPCs中β-连环蛋白和端粒酶逆转录酶(TERT)蛋白的表达水平。

结论

药物靶点调节的结果表明,与不同提取方案相关的内酯组成显著影响提取物的药理潜力,并指出不仅要标准化总内酯含量,还要标准化内部内酯比例的价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/762f53d673e0/JNME2023-9599744.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/c977197bd585/JNME2023-9599744.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/9398f18043a7/JNME2023-9599744.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/5a3552f60ad8/JNME2023-9599744.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/762f53d673e0/JNME2023-9599744.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/c977197bd585/JNME2023-9599744.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/9398f18043a7/JNME2023-9599744.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/5a3552f60ad8/JNME2023-9599744.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4c3d/10560109/762f53d673e0/JNME2023-9599744.004.jpg

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