Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis

Abstract

Objectives. Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney. Conclusion. Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

Methanol extract of Myelophycus caespitosus ameliorates oxidative stress-induced cytotoxicity in C2C12 murine myoblasts via activation of heme oxygenase-1

“…These findings indicate that discovering substances that can activate the Nrf2/HO-1 axis might be one of the appropriate strategies to counteract cellular damage caused by oxidative stress. Recently, numerous studies have suggested that various natural products have antioxidant properties that can inhibit oxidative damage-mediated apoptosis in myoblasts through activation of the Nrf2/HO-1 signaling (Rui et al, 2022;Wu et al, 2022;Xu et al, 2021;Zhang et al, 2021). Therefore, we investigated whether MEMC could activate Nrf2 and found that the level of p-Nrf2 expression indicating that Nrf2 was activated was clearly upregulated by H 2 O 2 in MEMC-pretreated C2C12 cells.…”

Novel Insight into Ferroptosis in Kidney Diseases

“…Other studies have indicated that irisin or ginsenoside Rg1 attenuates AKI in septic mice through anti-ferroptosis in renal tubular epithelial cells [39, 116]. Some alkaloids, such as pyrazine alkaloids, isoquinoline alkaloids, pyrimidine alkaloids, tropane alkaloids, carbine alkaloids, organic amine alkaloids, and aporphine alkaloids, originating from various Chinese herbs, are crucial in the treatment of AKI [117]. Scientific evidence has also suggested that inhibiting ATF3 expression and halting ferroptosis in renal proximal tubular epithelial cells are two mechanisms by which low-dose quercetin (10 mg/kg) ameliorates AKI [118].…”

Potential therapeutic effects of Chinese meteria medica in mitigating drug-induced acute kidney injury

“…At present, Chinese medicine has received strong support from the World Health Organization and is included in Chapter 26 of the 11th edition of the Global Medical Program. The renoprotective effects of some Chinese medicinal formulas and metabolites have received widespread attention and have been studied in multiple AKI models, including DI-AKI ( Wang et al, 2019 ; Li and Gong, 2022 ; Rui et al, 2022 ; Zou et al, 2022 ). In this review, whether Chinese meteria medica and their preparations or monomers can improve DI-AKI and their potential mechanisms of action were explored.…”