Publications by authors named "Yaoxing Dou"

4 Publications

  • Page 1 of 1

Oxyberberine, an absorbed metabolite of berberine, possess superior hypoglycemic effect via regulating the PI3K/Akt and Nrf2 signaling pathways.

Biomed Pharmacother 2021 May 30;137:111312. Epub 2021 Jan 30.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, PR China. Electronic address:

Berberine (BBR) is a promising anti-diabetic isoquinoline alkaloid from Rhizoma coptidis, while its bioavailability was extremely low. Here, the existing form and pharmacokinetics of BBR were comparatively characterized in conventional and antibiotic-induced pseudo germ-free (PGF) rats. Furthermore, we comparatively investigated the antidiabetic effect and potential mechanism of BBR and its intestinal oxidative metabolite oxyberberine (OBB) in STZ-induced diabetic rats. Results showed that BBR and OBB existed mainly as protein-bound form in blood, while protein-bound OBB was significantly depleted in PGF rats. Treatment with OBB and BBR effectively decreased clinical symptoms of diabetic rats, reduced blood glucose level, ameliorated the pancreatic damage, and mitigated oxidative stress and inflammatory markers. However, the anti-diabetes effect of BBR was obviously compromised by antibiotics. In addition, OBB exerted superior anti-diabetes effect to BBR of the same dose, significantly up-regulated the mRNA expression of Nrf2 signaling pathway and substantially promoted the pancreatic levels of PI3K/Akt signaling pathway. In conclusion, BBR and its absorbed oxidative metabolite OBB were mainly presented and transported in the protein-bound form in vivo. The gut microbiota may play an important role in the anti-diabetes effect of BBR through transforming itself into the superior hypoglycemic metabolite OBB. OBB possessed favorable hypoglycemic and pancreatic β-cells protective effects, which may stand a huge potential to be further developed into a promising anti-diabetes candidate.
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http://dx.doi.org/10.1016/j.biopha.2021.111312DOI Listing
May 2021

The anti-hepatocellular carcinoma effect of Brucea javanica oil in ascitic tumor-bearing mice: The detection of brusatol and its role.

Biomed Pharmacother 2021 Feb 16;134:111122. Epub 2020 Dec 16.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, PR China. Electronic address:

Brucea javanica oil (BJO), one of the main products of Brucea javanica, has been widely used in treating different kinds of malignant tumors. Quassinoids are the major category of anticancer phytochemicals of B. javanica. However, current researches on the anti-cancer effect of BJO mainly focused on oleic acid and linoleic acid, the common major components of dietary edible oils, essential and characteristic components of B. javanica like quassinoids potentially involved remained unexplored. In the current investigation, we developed an efficient HPLC method to detect brusatol, a characteristic quassinoid, and comparatively scrutinized the anti-hepatocellular carcinoma (anti-HCC) effect of BJO, brusatol-free BJO (BF-BJO), and brusatol-enriched BJO (BE-BJO) against hepatoma 22 (H22) in mice. High-performance liquid chromatography (HPLC) was utilized to identify the components in BJO. BE-BJO was extracted with 95 % ethanol. The anti-tumor effect of BJO, BF-BJO and BE-BJO was comparatively investigated, and the potential underlying mechanism was explored in H22 ascites tumor-bearing mice. The results indicated that BJO and BE-BJO significantly prolonged the survival time of H22 ascites tumor-bearing mice, while BF-BJO exhibited no obvious effect. BJO and BE-BJO exhibited pronounced anti-HCC activity by suppressing the growth of implanted hepatoma H22 in mice, including ascending weight, abdominal circumference, ascites volume and cancer cell viability, with a relatively wide margin of safety. BJO and BE-BJO significantly induced H22 cell apoptosis by upregulating the miRNA-29b gene level and p53 expression. Furthermore, BJO and BE-BJO treatment substantially downregulated Bcl-2 and mitochondrial Cytochrome C protein expression, and upregulated expression levels of Bax, Bad, cytosol Cytochrome C, caspase-3 (cleaved), caspase‑9 (cleaved), PARP and PARP (cleaved) to induce H22 cells apoptosis. Brusatol was detected in BJO and found to be one of its major active anti-HCC components, rather than fatty acids including oleic acid and linoleic acid. The anti-HCC effect of BJO and BE-BJO was intimately associated with the activation of miRNA-29b, p53-associated apoptosis and mitochondrial-related pathways. Our study gained novel insight into the material basis of BJO in the treatment of HCC, and laid a foundation for a novel specific standard for the quality evaluation of BJO and its commercial products in terms of its anti-cancer application.
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http://dx.doi.org/10.1016/j.biopha.2020.111122DOI Listing
February 2021

Brusatol ameliorates 2, 4, 6-trinitrobenzenesulfonic acid-induced experimental colitis in rats: Involvement of NF-κB pathway and NLRP3 inflammasome.

Int Immunopharmacol 2018 Nov 13;64:264-274. Epub 2018 Sep 13.

Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China. Electronic address:

Brusatol is a main bioactive component derived from the Chinese medicinal plant Brucea javanica, which is traditionally used for the treatment of dysentery (also known as ulcerative colitis, UC). Previously, we have designed a novel brusatol self-microemulsifying drug delivery system (BR-SMEDDS) to increase its solubility and bioavailability, and enhance its bioactivities. In the present study, we established 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model in vivo and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro, to investigate the potential anti-inflammatory effect and underlying mechanism of BR-SMEDDS. Disease activity index (DAI) including body weight, stool consistency and gross bleeding was measured. Macroscopic and histological evaluations of colons were conducted. Relevant molecular events were determined by ELISA, qRT-PCR, immunohistochemistry or Western blotting. The results showed that BR notably inhibited the productions of TNF-α, pro-IL-1β, PGE and NO, and suppressed the NF-κB signaling pathway in LPS-stimulated macrophages. In parallel with the vitro experimental results, BR significantly attenuated diarrhea, colonic shortening, macroscopic damage and histological injury. BR treatment also increased the levels of TGF-β and IL-4, decreased the contents of IL-1β and IL-18, and elevated the levels of CAT, GSH and SOD in the colons. Furthermore, BR also markedly activated the Nrf2 expression and suppressed the NLRP3 inflammasome activation. Taken together, the anti-UC effect of BR might be intimately associated with the suppression of NF-κB and NLRP3-mediated inflammatory responses, and regulation of Nrf2-mediated oxidative stress. BR might have the potential to be further developed into a promising therapeutic agent for colitis treatment.
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http://dx.doi.org/10.1016/j.intimp.2018.09.008DOI Listing
November 2018

Prophylactic efficacy of patchoulene epoxide against ethanol-induced gastric ulcer in rats: Influence on oxidative stress, inflammation and apoptosis.

Chem Biol Interact 2018 Mar 12;283:30-37. Epub 2018 Jan 12.

Shenzhen Key Laboratory of Hospital Chinese Medicine Preparation, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China. Electronic address:

Patchoulene epoxide (PAO), a tricyclic sesquiterpene isolated from the long-stored patchouli oil, has been demonstrated the anti-inflammatory activity in vivo based on our previous study. However, the gastric protective effect of PAO still remains unknown. Therefore, in the present study, ethanol-induced gastric ulcer model was carried out to evaluate the anti-ulcerogenic activity of PAO and to elucidate the potential mechanisms that involves. According to our results, macroscopic examination revealed that PAO could significantly reduce ethanol-induced gastric ulcer areas as compared with the vehicle group, which was also supported by the histological evaluation result. As for its potential mechanism, the anti-inflammatory activity of PAO contributed to gastric protection through reversing the imbalance between pro- and anti-inflammatory cytokines and modulating the expressions of NF-κB pathway-related proteins including p-IκBα, IκBα, p-p65 and p65. Besides, PAO was able to enhance the expressions of antioxidant enzymes including glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and down-regulate malonaldehyde (MDA), an indicator of lipid peroxidation. Furthermore, immunohistochemistry analysis exhibited potent anti-apoptosis effect of PAO, as evidence by down-regulating the protein expression of caspase-3, Fas and Fasl. Additionally, we also demonstrated that PAO could replenish PGE and NO mucosal defense. In conclusion, these findings suggested that PAO has gastric protective activity against ethanol and this might be related to its influence on inflammatory response, oxidative stress, apoptosis cascade and gastric mucosal defense.
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http://dx.doi.org/10.1016/j.cbi.2018.01.014DOI Listing
March 2018
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