Therapeutic effects of kaempferol affecting autophagy and endoplasmic reticulum stress

Abstract

Regulated cell death (RCD) guarantees to preserve organismal homeostasis. Apoptosis and autophagy are two major arms of RCD, while endoplasmic reticulum (ER) as a crucial organelle involved in proteostasis, promotes cells toward autophagy and apoptosis. Alteration in ER stress and autophagy machinery is responsible for a great number of diseases. Therefore, targeting those pathways appears to be beneficial in the treatment of relevant diseases. Meantime, among the traditional herb medicine, kaempferol as a flavonoid seems to be promising to modulate ER stress and autophagy and exhibits protective effects on malfunctioning cells. There are some reports indicating the capability of kaempferol in affecting autophagy and ER stress. In brief, kaempferol modulates autophagy in noncancerous cells to protect cells against malfunction, while it induces cell mortality derived from autophagy through the elevation of p-AMP-activated protein kinase, light chain-3-II, autophagy-related geness, and Beclin-1 in cancer cells. Noteworthy, kaempferol enhances cell survival through C/EBP homologous protein (CHOP) suppression and GRP78 increment in noncancerous cells, while it enhances cell mortality through the induction of unfolding protein response and CHOP increment in cancer cells. In this review, we discuss how kaempferol modulates autophagy and ER stress in noncancer and cancer cells to expand our knowledge of new pharmacological compounds for the treatment of associated diseases. K E Y W O R D S apoptosis, autophagy, cell death, endoplasmic reticulum stress, flavonoid, kaempferol

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Exploring the Potential Mechanism of Guchang Zhixie Wan for Treating Ulcerative Colitis by Comprehensive Network Pharmacological Approaches and Molecular Docking Validation as Well as Cell Experiments

“…Quercetin, β‐sitosterol and kaempferol are common compounds found in many herbal medicines. Many scientific reports recognized that they possess antinociceptive, anxiolytic and sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, anti‐inflammatory, protective effects on respiratory diseases, wound‐healing effects, antioxidants, and so on [26–31] . Because of their numerous biological functions, they are considered as biologically active compounds and have been studied for the treatment of diseases through network pharmacology methods.…”

“…Many scientific reports recognized that they possess antinociceptive, anxiolytic and sedative effects, analgesic, immunomodulatory, antimicrobial, anticancer, antiinflammatory, protective effects on respiratory diseases, wound-healing effects, antioxidants, and so on. [26][27][28][29][30][31] Because of their numerous biological functions, they are considered as biologically active compounds and have been studied for the treatment of diseases through network pharmacology methods. Moreover, molecular docking analyses indicated that the binding forces between drug compounds (quercetin, β-sitosterol and kaempferol) and six UC-related proteins (IFN, IL1A, IL1B, JUN, RELA and STAT1) were very strong.…”

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