Poricoic acid A(F)

Zhongcaoyao, 2017(9):328.

Tyrosinase Inhibitory Activity of Total Triterpenes and Poricoic Acid A Isolated from Poria cocos.[Reference: WebLink]

With the improvement of people's living standards, people's requests for beauty are increasing. Skin whitening and lightening have become the pursuit of many women, and whitening and removing freckles have become the focus of scientific research. At present, widely used whitening agents, such as kojic acid, vitamin C, and its derivatives, have shortcomings such as poor stability and retarded effect. Therefore, safer and more effective whitening products from herbs are urgently needed. To explore the possibility of triterpenes as whitening active substance, the effects of total triterpenes of Poria (TTP) and Poricoic acid A(F) (PAA) on mushroom tyrosinase activities and B16 cells were investigated, and their mechanisms on mushroom tyrosinase were also studied.
METHODS AND RESULTS:
Using arbutin and nicotinamide as reference substances, we determinated the inhibitory effects of TTP and PAA on mushroom tyrosinase and tyrosinase in B16 cells and then studied the inhibitory mechanism on mushroom tyrosinase. TTP and PAA exhibited good inhibitory effects on the activities of monophenolase and diphenolase in mushroom tyrosinase, as well as a certain inhibitory effect on tyrosinase in B16 cells.
CONCLUSIONS:
TTP and PAA are potential whitening active ingredients.

Journal of Natural Products, 2011, 74(2):137-144.

Cytotoxic and Apoptosis-Inducing Activities of Triterpene Acids from Poria cocos.[Reference: WebLink]

METHODS AND RESULTS:
Six lanostane-type triterpene acids (1a-6a), isolated from Poria cocos , and their methyl ester (1b-6b) and hydroxy derivatives (1c-6c) were prepared. Upon evaluation of the cytotoxic activity of these compounds against leukemia (HL60), lung (A549), melanoma (CRL1579), ovary (NIH:OVCAR-3), breast (SK-BR-3), prostate (DU145), stomach (AZ521), and pancreas (PANC-1) cancer cell lines, 11 compounds (5a, 6a, 2b-5b, 1c, and 3c-6c) exhibited activity with single-digit micromolar IC(50) values against one or more cell lines. Poricotriol A (1c), a hydroxy derivative of Poricoic acid A(F) (1a), exhibited potent cytotoxicities against six cell lines with IC(50) values of 1.2-5.5 μM. poricotriol Ainduced typical apoptotic cell death in HL60 and A549 cells on evaluation of the apoptosis-inducing activity by flow cytometric analysis. Western blot analysis in HL60 cells showed that poricotriol A activated caspases-3, -8, and -9, while increasing the ratio of Bax/Bcl-2.
CONCLUSIONS:
This suggested that poricotriol A induced apoptosis via both mitochondrial and death receptor pathways in HL60. On the other hand, poricotriol A did not activate caspases-3, -8, and -9, but induced translocation of apoptosis-inducing factor (AIF) from mitochondria and increased the ratio of Bax/Bcl-2 in A549. This suggested that poricotriol A induced apoptosis via the mitochondrial pathway mostly by translocation of AIF, independent from the caspase pathway in A549. Furthermore, poricotriol A was shown to possess high selective toxicity in lung cancer cells since it exhibited only weak cytotoxicity against a normal lung cell line (WI-38).

Free Radic Biol Med . 2019 Apr;134:484-497.

Poricoic acid A enhances melatonin inhibition of AKI-to-CKD transition by regulating Gas6/AxlNFκB/Nrf2 axis[Pubmed: 30716432]

Abstract Renal ischemia-reperfusion injury (IRI) is a complex syndrome, which causes chronic kidney disease (CKD) after recovery from IRI-mediated acute kidney injury (AKI). There is no single therapy that could effectively prevent the renal injury after ischemia. In this study, the effects of melatonin or poricoic acid A (PAA) and their combination were investigated in protecting against AKI-to-CKD transition in rats and hypoxia/reoxygenation (H/R)-induced injury in cultured renal NRK-52E cells. Melatonin and PAA significantly reduced the magnitude of rise in serum creatinine and urea levels in IRI rats at days 3 and 14. Our results further showed that treatment with melatonin and PAA ameliorated renal fibrosis and podocyte injury by attenuating oxidative stress and inflammation via regulation of nuclear factor-kappa B (NF-κB) and nuclear factor-erythroid-2-related factor 2 (Nrf2) pathways in IRI rats. Melatonin and PAA protected against AKI-to-CKD transition by regulating growth arrest-specific 6 (Gas6)/AxlNFκB/Nrf2 signaling cascade. Melatonin and PAA initiallyupregulated Gas6/Axl signaling to reduce oxidative stress and inflammation in AKI and subsequently downregulated Gas6/Axl signaling to attenuate renal fibrosis and progression to CKD. Melatonin and PAA inhibited expression of extracellular matrix proteins. Poricoic acid A enhances melatonin-mediated inhibition of AKI-to-CKD transition by the regulating Gas6/AxlNFκB/Nrf2 signaling cascade. Notably, our study first identified Axl as a promising therapeutic target for prevention of AKI-to-CKD transition. Keywords: Acute kidney injury; Chronic kidney disease; Gas6/Axl; Inflammation and oxidative stress; Melatonin; Poria cocos; Poricoic acid A.

Phytotherapy Research, 1996, 10(7):581-584.

Inhibitory Effect of Poria cocos on 12‐O‐Tetradecanoylphorbol‐13‐Acetate‐Induced Ear Oedema and Tumour Promotion in Mouse Skin.[Reference: WebLink]

METHODS AND RESULTS:
The methanol extract from the sclerotium of Poria cocos was found to inhibit 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced tumour promotion in two-stage carcinogenesis in mouse skin. From the active fraction of the extract, eight lanostane-type triterpene acids and four 3,4-secolanostane-type triterpene acids were isolated. The isolated compounds showed inhibitory activity against TPA-induced ear inflammatory oedema.
CONCLUSIONS:
The 50% inhibitory dose of pachymic acid, 3- O -acetyl-16α-hydroxytrametenolic acid, dehydropachymic acid, dehydroeburiconic acid, 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid, Poricoic acid A(F) and poricoic acid B for TPA-induced inflammation was 17–44 μg/ear, at a grade corresponding to that of hydrocortisone.