Poricoic acid A induces apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis

Ma, Rui; Zhang, Zhenhua; Xu, Jianhua; Liang, Ximing; Zhao, Qiang

doi:10.1590/1414-431x2021e11183

Cited by 9 publications

(10 citation statements)

References 24 publications

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“…Also, the specific interaction between PAA and NF- κ B/MAPK signaling pathway required further investigation. Additionally, as a formulated drug, “ Poria cocos polysaccharide oral solution” was approved by the China Food and Drug Administration in 2015 for the treatment of various types of cancer, hepatitis, and other diseases, and “ Poria cocos polysaccharide oral solution” can be applied alone or during chemoradiation for the treatment of cancer [ 11 , 32 ]. Further improvement of the above experiments will be expected to provide strong support for PAA in the treatment of CRS.…”

Section: Discussionmentioning

confidence: 99%

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Poricoic Acid A Inhibits the NF-κB/MAPK Pathway to Alleviate Renal Fibrosis in Rats with Cardiorenal Syndrome

Chen

Zhang²,

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. To explore the potential and mechanism of action of poricoic acid A (PAA) in treatment of cardiorenal injury and fibrosis due to cardiorenal syndrome (CRS). Materials and Methods. A CRS rat model was established by transabdominal subtotal nephrectomy (STNx). The experimental group was treated by gavage of PAA (10 mg/kg/day). After 8 weeks of treatment, echocardiography was utilized for detecting heart-related indexes in rats. HE and Masson staining were conducted to detect the degree of pathological damage and fibrosis in rat kidney tissue, respectively. In addition, serum blood urea nitrogen (BUN), serum creatinine (SCr), and 24-hour urine protein were measured biochemically. Also, the levels of inflammatory factors (IL-1β, IL-6, and IL-10) in rat kidneys were measured using ELISA. Western blot was used to examine the expression of NF-κB/MAPK pathway-related proteins. Results. In this study, a CRS rat model was successfully established by STNx surgery. PAA treatment could significantly alleviate the damage of heart and kidney function in CRS rats and reduce the pathological damage of kidney tissue and renal fibrosis. Meanwhile, PAA could also inhibit the renal inflammatory response through downregulating IL-1β and IL-6 levels in the kidney tissue and upregulating IL-10 level. Further mechanism exploration showed that the NF-κB/MAPK signaling pathway was significantly activated in CRS rats, while PAA treatment could markedly inhibit the NF-κB/MAPK signaling pathway activity in CRS rats. Conclusion. PAA can obviously improve the pathological damage and fibrosis of renal tissue in CRS rats and maintain the function of the heart and kidney. The above functions of PAA may be achieved by inhibiting the NF-κB/MAPK signaling pathway activity. Briefly speaking, PAA can serve as a potential drug for CRS treatment.

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Section: Discussionmentioning

confidence: 99%

“…Studies have also revealed anticancer effects of PAA. For example, Ma et al found that PAA could inhibit the proliferation, migration, and invasion of ovarian cancer cells SKOV3 and induce apoptosis and autophagy of cancer cells [ 11 ]. In addition, PAA plays an important role in a variety of kidney-related diseases.…”

Section: Introductionmentioning

confidence: 99%

Poricoic Acid A Inhibits the NF-κB/MAPK Pathway to Alleviate Renal Fibrosis in Rats with Cardiorenal Syndrome

Chen

Zhang²,

Huang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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“…TS, WSP, and AP are the three major active ingredients in PC. For example, TS has been proven to exert potent pharmacological effects [ 3 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], such as anti-inflammatory, anti-tumor, and diuretic effects [ 6 , 7 , 8 ]. Polysaccharides have liver-protective, immune-boosting, and anti-aging effects [ 28 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Quantification of Chemical Groups and Quantitative HPLC Fingerprint of Poria cocos (Schw.) Wolf

Huang

Jiang

et al. 2022

Molecules

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(1)Objective: In this study, a quantitative analysis of chemical groups (the triterpenoids, water-soluble polysaccharides, and acidic polysaccharides) and quantitative high liquid performance chromatography (HPLC) fingerprint of Poria cocos (Schw.) Wolf (PC) for quality control was developed. (2) Methodology: First, three main chemical groups, including triterpenoids, water-soluble polysaccharides, and acidic polysaccharides, in 16 batches of PC were evaluated by ultraviolet spectrophotometry. Afterward, the quantitative fingerprint of PC was established, and the alcohol extract of PC was further evaluated. The method involves establishing 16 batches of PC fingerprints by HPLC, evaluating the similarity of different batches of PC, and identifying eight bioactive components, including poricoic acid B (PAB), dehydrotumulosic acid (DTA), poricoic acid A (PAA), polyporenic acid C (PAC), 3-epidehydrotumulosic acid (EA), dehydropachymic acid (DPA), dehydrotrametenolic acid (DTA-1), and dehydroeburicoic acid (DEA), in PC by comparison with the reference substance. Combined with the quantitative analysis of multi-components by a single marker (QAMS), six bioactive ingredients, including PAB, DTA, PAC, EA, DPA, and DEA, in PC from different places were established. In addition, the multivariate statistical analyses, such as principal component analysis and heatmap hierarchical clustering analysis are more intuitive, and the visual analysis strategy was used to evaluate the content of bioactive components in 16 batches of PC. Finally, the analysis strategy of three main chemical groups in PC was combined with the quantitative fingerprint strategy, which reduced the error caused by the single method. (3) Results: The establishment of a method for the quantification of chemical groups and quantitative HPLC fingerprint of PC was achieved as demonstrated through the quantification of six triterpenes in PC by a single marker. (4) Conclusions: Through qualitative and quantitative chemical characterization, a multi-directional, simple and efficient routine evaluation method of PC quality was established. The results reveal that this strategy can provide an analytical method for the quality evaluation of PC and other Chinese medicinal materials.

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“…Furthermore, a recent study showed that overexpression of the long-chain non-coding RNA H19 downregulated miR-140–5p and activated the PI3K/AKT signaling pathway to promote OC cell invasion, migration, and epithelial-mesenchymal transition ( Xu et al, 2021 ). Previous studies have found that poricoic acid A, the main component of Poria cocos , can induce apoptosis in ovarian cancer cells by regulating the mTOR/p70s6k signaling axis ( Ma et al, 2021 ). And our research has identified another important active component of Poria cocos , so we want to further explore the anticancer effect of tumulosic acid, and compare the effects of poricoic acid A with tumulosic acid.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Pharmacological Mechanism of Poria cocos-Based Formulas Combined With Chemotherapy for Ovarian Cancer: A Integrated Systems Pharmacology Study

et al. 2022

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Previous studies have shown that Poria cocos-based formulas combined with chemotherapy can improve the quality of life of ovarian cancer patients. However, the results are still controversial. We systematically searched the literature from eight databases to evaluate the efficacy and safety of Poria cocos-based formulas in combination with paclitaxel-carboplatin in treating ovarian cancer (OC). Subsequently, network pharmacology, molecular docking and cell experiments were performed to further verify the underlying molecular mechanism. Thirteen randomized controlled trials, including 922 patients with OC, were enrolled in the study. The results indicated that Poria cocos-based compounds combined with paclitaxel-carboplatin significantly improved patients’ tumor response rate, traditional Chinese medicine syndrome score, Karnofsky Performance Scale, physical and social function, and reduced side effects of chemotherapy compared to the paclitaxel-carboplatin alone. According to the network pharmacological analysis, tumulosic acid were the most bioactive compounds of Poria cocos. BCL2L1 is highly expressed in OC and is associated with a worse prognosis which could become potential drug target. Functional enrichment analysis suggested that the anti-OC effect of Poria cocos may be related to PI3K-Akt signaling pathway. The molecular docking results indicated that tumulosic acid might inhibit OC by regulating BCL2L1. Vitro experiment confirmed tumulosic acid that induced cell apoptosis by modulating PI3K/AKT signaling and BCL2L1. Our study may provide a clinical basis and theoretical rationale for combining Poria cocos-based formulas with chemotherapy for OC. In addition, the integrated pharmacological strategy proposed in our study provides an excellent example for exploring the mechanism of complex formulas.

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Poricoic acid A induces apoptosis and autophagy in ovarian cancer via modulating the mTOR/p70s6k signaling axis

Cited by 9 publications

References 24 publications

Poricoic Acid A Inhibits the NF-κB/MAPK Pathway to Alleviate Renal Fibrosis in Rats with Cardiorenal Syndrome

Poricoic Acid A Inhibits the NF-κB/MAPK Pathway to Alleviate Renal Fibrosis in Rats with Cardiorenal Syndrome

Quantification of Chemical Groups and Quantitative HPLC Fingerprint of Poria cocos (Schw.) Wolf

Efficacy and Pharmacological Mechanism of Poria cocos-Based Formulas Combined With Chemotherapy for Ovarian Cancer: A Integrated Systems Pharmacology Study

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