Abstract

Indole alkaloids are widely distributed in nature and have been particularly studied because of their diverse biological activities, such as anti-inflammatory, anti-tumor, anti-bacterial, and anti-oxidant activities. Many kinds of indole alkaloids have been applied to clinical practice, proving that indole alkaloids are beneficial scaffolds and occupy a crucial position in the development of novel agents. Fibrosis is an end-stage pathological condition of most chronic inflammatory diseases and is characterized by excessive deposition of fibrous connective tissue components, ultimately resulting in organ dysfunction and even failure with significant morbidity and mortality. Indole alkaloids and indole derivatives can alleviate pulmonary, myocardial, renal, liver, and islet fibrosis through the suppression of inflammatory response, oxidative stress, TGF-β/Smad pathway, and other signaling pathways. Natural indole alkaloids, such as isorhynchophylline, evodiamine, conophylline, indirubin, rutaecarpine, yohimbine, and vincristine, are reportedly effective in organ fibrosis treatment. In brief, indole alkaloids with a wide range of pharmacological bioactivities are important candidate drugs for organ fibrosis treatment. The present review discusses the potential of natural indole alkaloids, semi-synthetic indole alkaloids, synthetic indole derivatives, and indole-contained metabolites in organ fibrosis treatment.

Highlights

  • Indole alkaloids are bicyclic nitrogenous compounds formed by the combination of six-membered benzene and five-membered pyrrole

  • The results proved that the inhibitory effect of rutaecarpine on hypoxic-induced right ventricular (RV) remodeling is stimulated by the release of calcitonin gene-related peptide (CGRP), and this effect may be associated with the eIF3a/p27 pathway (Li et al, 2016)

  • The current review summarizes the recent advancements in the use of indole alkaloids and indole derivatives to treat organ fibrosis

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Summary

INTRODUCTION

Indole alkaloids are bicyclic nitrogenous compounds formed by the combination of six-membered benzene and five-membered pyrrole. In an anti-fibrotic screening of indole alkaloid compound library, Li et al found that matrine derivative compound 3f could attenuate idiopathic pulmonary fibrosis via suppression of fibroblast-tomyofibroblast transition and inhibition of the TGF-β/Smad signaling pathway. Indole-3carbinol (I3C), an indole alkaloidal compound extracted from cruciferous vegetables, reported that by activating the AhRresponsive genes in rat lungs, the pup’s lung injury induced by hyperoxia-hypoxia was alleviated, thereby improving alveolarization and decreasing fibrosis In their experiments, I3C could activate TNF-α and NF-κB pathway to promote the expressions of VEGF, MCP1, MMP-8, and IL-6 and regulate inflammatory processes. Found that isorhy prevented phenylephrine (PE)-induced myocardial hypertrophy and alleviated myocardial fibrosis in rats by inhibiting the expressions of TGF-β1, CTGF, and collagen I/III and other related fibrosis factors These effects were associated with Nrf nuclear translocation and MAPK pathway (Zhang et al, 2020b). Results of experiments on a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model, showed that treatment with yohimbine significantly decreased urinary protein excretion

CONCLUSION AND OUTLOOKS
Findings
DATA AVAILABILITY STATEMENT

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