Puerarin prevents cadmium-induced hepatic cell damage by suppressing apoptosis and restoring autophagic flux

et al. 2021

Front. Pharmacol.

Autophagic dysfunction is one of the main mechanisms by which the environmental pollutant cadmium (Cd) induces cell injury. Puerarin (Pue, a monomeric Chinese herbal medicine extract) has been reported to alleviate Cd-induced cell injury by regulating autophagy pathways; however, its detailed mechanisms are unclear. In the present study, to investigate the detailed mechanisms by which Pue targets autophagy to alleviate Cd hepatotoxicity, alpha mouse liver 12 (AML12) cells were used to construct a model of Cd-induced hepatocyte injury in vitro. First, the protective effect of Pue on Cd-induced cell injury was confirmed by changes in cell proliferation, cell morphology, and cell ultrastructure. Next, we found that Pue activated autophagy and mitigated Cd-induced autophagy blockade. In this process, the lysosome was further activated and the lysosomal degradation capacity was strengthened. We also found that Pue restored the autophagosome-lysosome fusion and the expression of Rab7 in Cd-exposed hepatocytes. However, the fusion of autophagosomes with lysosomes and autophagic flux were inhibited after knocking down Rab7, and were further inhibited after combined treatment with Cd. In addition, after knocking down Rab7, the protective effects of Pue on restoring autophagosome-lysosome fusion and alleviating autophagy blockade in Cd-exposed cells were inhibited. In conclusion, Pue-mediated alleviation of Cd-induced hepatocyte injury was related to the activation of autophagy and the alleviation of autophagy blockade. Pue also restored the fusion of autophagosomes and lysosomes by restoring the protein expression of Rab7, thereby alleviating Cd-induced autophagy blockade in hepatocytes.

Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 57%

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Puerarin Restores Autophagosome-Lysosome Fusion to Alleviate Cadmium-Induced Autophagy Blockade via Restoring the Expression of Rab7 in Hepatocytes

Wang

et al. 2021

Front. Pharmacol.

“…Previous studies also have shown that animals treated with both Cd and PU have better kidney function and less pathological damage than those treated with cadmium alone 43 . PU can reduce cadmium‐induced hepatocyte and renal cell injury by inhibiting apoptosis and restoring autophagy activity 45,46 . In addition, PU can significantly restore the level of antioxidant enzymes in the kidney, which may be related to the restoration of mitochondrial function 43 .…”

Section: Discussionmentioning

confidence: 95%

Puerarin prevents cadmium‐induced disorder of testicular lactic acid metabolism in rats by activating 5′AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway

Dong

Environmental Toxicology

Liu

et al. 2021

Cadmium (Cd) interferes with the function of the male reproductive system; however, the molecular mechanism is poorly understood. This study aimed to evaluate the effect of puerarin (PU) on Cd‐induced testicular lactic acid metabolism disorder. Weaning male Sprague–Dawley rats were pre‐fed for 7 days, weighed, and randomly divided into four groups: Control group, CdAc2 group, CdAc2 + PU group, PU group. The results showed that Cd accumulated in the testis, the testicles became congested and shrank, and the testis index decreased in the rats treated in the CdAc2 group. Cadmium exposure reduced the serum concentration of testosterone, and the concentration of lactic acid and pyruvate in the testis. Cd decreased testicular superoxide dismutase activity and total antioxidant capacity, and increased testicular malondialdehyde levels. Cd reduced the level of ATP, glycolytic gene expression, and lactate production‐related proteins in the testis. Cd also decreased the expression of 5′ AMP‐activated protein kinase (AMPK)/sirtuin 1 (SIRT1) signaling pathway‐related proteins in the testis. However, these negative effects were attenuated by PU administration. In summary, Cd reduces the production of lactic acid in the testis of rats, while PU administration restores the production of lactic acid and reduces the toxicity of Cd to the testis of rats.

“…In addition, a considerable number of studies suggested that Puerarin could regulate the autophagic activity. Some reports have shown that Puerarin upregulates autophagy [11–13], but some studies showed that it inhibits autophagy [14–16]. He et al [14] suggested that Puerarin had neuroprotective effect against cerebral ischemia, which was related to the decrease of autophagic activity in neurons after its intervention.…”

Section: Introductionmentioning

confidence: 99%

Puerarin inhibits the osteoclastogenesis by inhibiting RANKL-dependent and –independent autophagic responses

BMC Complement Altern Med

Wang

Tang

et al. 2019

Background Puerarin exerts therapeutic effect on osteoporosis due to its inhibitory effect on the formation of osteoclasts. Puerarin is also widely established as an autophagy inhibitor. The study aimed to investigate the significance of autophagy in Puerarin-treated osteoclast formation. Methods Osteoclast precursors (OCPs) derived from bone marrow-derived macrophages (BMMs) were treated with Puerarin along with RANKL or without RANKL, and then the autophagic parameters of OCPs (including autophagic proteins, LC3 transformation, autophagosome or LC3-puncta) were observed through Western Blotting, Transmission Electron Microscopy and Immunofluorescence assays. Next, after using overexpression vectors of autophagic genes (Atg7, Atg5 and BECN1) to alter autophagy activity, OCP proliferation was measured by Ethynyl deoxyuridine (EdU) assays and Cell Counting Kit-8 (CCK-8) kit, and osteoclast differentiation was assessed by Tartrate-resistant acid phosphatase (TRAP) staining. Results The results showed that Puerarin could directly inhibit the autophagy and proliferation of OCPs. Importantly, overexpression of autophagic genes Atg5, Atg7 and BECN1 reversed Puerarin-inhibited OCP autophagy and proliferation. What’s more, RANKL could promote the autography of OCPs, which was recovered by Puerarin treatment. Interestingly, different from single-Puerarin treatment, we found that in the presence of RANKL, only BECN1 overexpression significantly reversed Puerarin-inhibited osteoclast differentiation and OCP autophagy. Conclusion In conclusion, Puerarin could inhibit the OCP autophagy in the presence or absence of RANKL, which blocked the OCP proliferation and osteoclast differentiation respectively. Moreover, BECN1 plays an essential role in Puerarin-inhibited osteoclastogenesis. Our study provides potential clue to further complete the intrinsic mechanism of Puerarin in treating osteoporosis.