Publications by authors named "Yucui Li"

22 Publications

  • Page 1 of 1

Genome assembly of the Chinese maize elite inbred line RP125 and its EMS mutant collection provide new resources for maize genetics research and crop improvement.

Plant J 2021 Jul 12. Epub 2021 Jul 12.

Maize Research Institute, Sichuan Agricultural University, ChengDu, 611130, China.

Maize is an important crop worldwide, as well as a valuable model with vast genetic diversity. Accurate genome and annotation information for a wide range of inbred lines would provide valuable resources for crop improvement and pan-genome characterization. In this study, we generated a high-quality de novo genome assembly (contig N50 of 15.43 megabases) of the Chinese elite inbred line RP125 using Nanopore long-read sequencing and Hi-C scaffolding, which yield highly contiguous, chromosome-length scaffolds. Global comparison of the RP125 genome with those of B73, W22, and Mo17 revealed a large number of structural variations. To create new germplasm for maize research and crop improvement, we carried out an EMS mutagenesis screen on RP125. We obtained a total of 5,818 independent M2 families, with 946 mutants showing heritable phenotypes. Taking advantage of the high-quality RP125 genome, we successfully cloned 10 mutants from the EMS library, including the novel kernel mutant qk1 (quekou: 'missing a small part' in Chinese), which exhibited partial loss of endosperm and a starch accumulation defect. QK1 encodes a predicted metal tolerance protein that is specifically required for iron transport. Increased accumulation of iron and ROS as well as ferroptosis-like cell death were detected in endosperm of qk1. Our study provides the community with a high-quality genome sequence and a large collection of mutant germplasm.
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http://dx.doi.org/10.1111/tpj.15421DOI Listing
July 2021

β-patchoulene protects against non-alcoholic steatohepatitis via interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation in rats.

Int Immunopharmacol 2021 Jun 29;98:107915. Epub 2021 Jun 29.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China; Dongguan & Guangzhou University of Chinese Medicine Cooperative Academy of Mathematical Engineering for Chinese Medicine, Dongguan 523808, China. Electronic address:

Non-alcoholic steatohepatitis (NASH), an extreme progressive subtype of metabolic associated fatty liver disease, is well characterized by hepatic steatosis, injury and inflammation. It causes irreversible hepatic damage and there are no approved interventions for it. β-PAE, a representatively pharmacological active substance isolated from Pogostemon cablin, has been indicated to alleviate hepatic steatosis and injury through modulating lipid metabolism in rats with simple steatosis. However, its protection against NASH remains unclear. Here, this study explored the potential effect of β-PAE against high-fat diet-induced NASH in rats. The results displayed that β-PAE significantly reduced the gains of body weight and epididymal adipose tissue, liver index and attenuated liver histological damages in NASH rats. It also markedly alleviated hepatic inflammation by inhibiting NLRP3 inflammasome activation. In NASH, the active NLRP3 inflammasome is caused by hepatic lipid abnormal accumulation-induced oxidative stress. Excessive oxidative stress results in hepatic histanoxia, which exacerbates lipid metabolism disorders by elevating CD36 to suppress AMPK signalling pathways. Moreover, the lipid accumulation led by lipid metabolism dysfunction intensifies oxidative stress. A vicious circle is formed among oxidative stress, histanoxia and lipid accumulation, eventually, but β-PAE effectively interrupted it. Interestingly, soluble CD36 (sCD36) was tightly associated not only with hepatic steatosis and injury but also with inflammation. Collectively, β-PAE exerted a positive effect against NASH by interrupting the vicious circle among oxidative stress, histanoxia and lipid accumulation, and sCD36 may be a promising non-invasive tool for NASH diagnosis.
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http://dx.doi.org/10.1016/j.intimp.2021.107915DOI Listing
June 2021

miR‑29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF‑β1 and p53 signaling pathway.

Int J Mol Med 2021 Aug 29;48(2). Epub 2021 Jun 29.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.

MicroRNA (miR)‑29b is a key tumor regulator. It can inhibit tumor cell proliferation, induce apoptosis, suppress tumor invasion and migration, thus delaying tumor progression. Our previous studies revealed an increased level of miR‑29b in hepatoma 22 (H22) cells in ascites tumor‑bearing mice. The present study investigated the effect of miR‑29b on proliferation and apoptosis of hepatocellular carcinoma ascites H22 cells and its association with the transforming growth factor‑β1 (TGF‑β1) signaling pathway and p53‑mediated apoptotic pathway. Briefly, H22 cells were transfected with miR‑29b‑3p (hereinafter referred to as miR‑29b) mimic or miR‑29b inhibitor. MTS cell proliferation assay and flow cytometry were used to analyze cell viability and apoptosis. The expression change of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway were detected by reverse transcription‑quantitative PCR, western blotting and immunofluorescence. Furthermore, cells were treated with exogenous TGF‑β1 and TGF‑β1 small interfering RNA to evaluate the crosstalk between TGF‑β1 and p53 under miR‑29b regulation. The overexpression of miR‑29b decreased cell viability, increased cell apoptosis, activated the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway. Conversely, these effects were reversed by the miR‑29b inhibitor. Moreover, the effect of miR‑29b mimic was further increased after treating cells with exogenous TGF‑β1. The activation of the TGF‑β1 signaling pathway and p53‑mediated apoptotic pathway induced by miR‑29b overexpression were reversed by TGF‑β1 inhibition. In summary, these data indicated that miR‑29b has an important role in proliferation and apoptosis of H22 cells by regulating the TGF‑β1 signaling pathway, the p53‑dependent apoptotic pathway, and the crosstalk between TGF‑β1 and p53.
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http://dx.doi.org/10.3892/ijmm.2021.4990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249050PMC
August 2021

Anti-Hyperuricemic and Nephroprotective Effects of Dihydroberberine in Potassium Oxonate- and Hypoxanthine-Induced Hyperuricemic Mice.

Front Pharmacol 2021 20;12:645879. Epub 2021 Apr 20.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Phellodendri Chinese Cortex has long been used to treat hyperuricemia and gout. Berberine (BBR), its characteristic ingredient, has also been shown to be effective in alleviating monosodium urate crystals-triggered gout inflammation and . Dihydroberberine (DHB) is a hydrogenated derivative of BBR that showed improved efficacy on many metabolic disorders. However, its anti-hyperuricemia effect remains underexplored. In the present work, the hypouricemic and renoprotective effects of DHB on hyperuricemic mice were investigated. The hyperuricemic mice model was induced by intraperitoneal injection of potassium oxonate (PO, 300 mg/kg) combined with intragastric administration of hypoxanthine (HX, 300 mg/kg) for 7 days. Different dosages of DHB (25, 50 mg/kg), BBR (50 mg/kg) or febuxostat (Feb, 5 mg/kg) were orally given to mice 1 h after modeling. The molecular docking results showed that DHB effectively inhibited xanthine oxidase (XOD) by binding with its active site. , DHB exhibited significant XOD inhibitory activity (IC value, 34.37 μM). The results showed that DHB had obvious hypouricemic and renoprotective effects in hyperuricemic mice. It could not only lower the uric acid and XOD levels in serum, but also suppress the activities of XOD and adenosine deaminase (ADA) in the liver. Furthermore, DHB noticeably down-regulated the renal mRNA and protein expression of XOD. Besides, DHB remarkably and dose-dependently ameliorated renal damage, as evidenced by considerably reducing serum creatinine and blood urea nitrogen (BUN) levels, inflammatory cytokine (TNF-α, IL-1β, IL-6 and IL-18) levels and restoring kidney histological deteriorations. Further mechanistic investigation showed that DHB distinctly down-regulated renal mRNA and protein levels of URAT1, GLUT9, NOD-like receptor 3 (NLRP3), apoptosis-associated speck-like (ASC), caspase-1 and IL-1β. Our study revealed that DHB had outstanding hypouricemic and renoprotective effects via suppressing XOD, URAT1, GLUT9 and NLRP3 inflammasome activation in the kidney.
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http://dx.doi.org/10.3389/fphar.2021.645879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093860PMC
April 2021

Gut Microbiota-Mediated Transformation of Coptisine Into a Novel Metabolite 8-Oxocoptisine: Insight Into Its Superior Anti-Colitis Effect.

Front Pharmacol 2021 30;12:639020. Epub 2021 Mar 30.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

Coptisine (COP) is a bioactive isoquinoline alkaloid derived from Franch, which is traditionally applied for the management of colitis. However, the blood concentration of COP was extremely low, and its gut microbiota-mediated metabolites were thought to contribute to its prominent bioactivities. To comparatively elucidate the protective effect and underlying mechanism of COP and its novel gut microbiota metabolite (8-oxocoptisine, OCOP) against colitis, we used dextran sulfate sodium (DSS) to induce colitis in mice. Clinical symptoms, microscopic alternation, immune-inflammatory parameters for colitis were estimated. The results indicated that OCOP dramatically ameliorated disease activity index (DAI), the shortening of colon length and colonic histopathological deteriorations. OCOP treatment also suppressed the mRNA expression and release of inflammatory mediators (TGF-β, TNF-α, IL-6, IL-18, IL-1β and IFN-γ) and elevated the transcriptional and translational levels of anti-inflammatory cytokine (IL-10) as well as the mRNA expression levels of adhesion molecules ( and ). Besides, the activation of NF-κB pathway and NLRP3 inflammasome was markedly inhibited by OCOP. Furthermore, OCOP displayed superior anti-colitis effect to COP, and was similar to MSZ with much smaller dosage. Taken together, the protective effect of OCOP against DSS-induced colitis might be intimately related to inhibition of NF-κB pathway and NLRP3 inflammasome. And the findings indicated that OCOP might have greater potential than COP to be further exploited as a promising candidate in the treatment of colitis.
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http://dx.doi.org/10.3389/fphar.2021.639020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042337PMC
March 2021

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

Coptisine ameliorates DSS-induced ulcerative colitis via improving intestinal barrier dysfunction and suppressing inflammatory response.

Eur J Pharmacol 2021 Apr 27;896:173912. Epub 2021 Jan 27.

Department of Pharmacology, Zunyi Medical University, Zhuhai Campus, Zhuhai, 519041, PR China. Electronic address:

Ulcerative colitis (UC), as an autoimmune disease, has been troubling human health for many years. Up to now, the available treatments remain unsatisfactory. Rhizoma Coptidis has been widely applied to treat gastrointestinal diseases in China for a long time, and coptisine (COP) is identified as one of its major active components. This study aimed to evaluate the bioactivity of COP on dextran sulfate sodium (DSS)-induced mice colitis and clarify the potential mechanism of action. The results revealed that COP treatment markedly alleviated DSS-induced clinical symptoms by relieving body weight loss and the disease activity index (DAI) score. Specifically, the colon length in the COP (50 and 100 mg/kg) groups were obviously longer than that in the DSS group (7.21 ± 0.34, 8.59 ± 0.45 cm vs. 6.71 ± 0.59 cm, P < 0.01). HE staining analysis revealed that COP treatment significantly protected the integrity of intestinal barrier and alleviated inflammatory cells infiltration. Western blot assay confirmed that COP notably improved the intestinal epithelial barrier function by enhancing the expressions of colonic tight junction proteins and inhibited the expressions of apoptosis-related proteins. In addition, COP treatment remarkably suppressed the levels of colonic myeloperoxidase (MPO), adhesion molecules and pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-17), while enhanced IL-10 and TGF-β. The mechanism anti-inflammatory of COP might be related to inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. In summary, the study indicated that COP ameliorated DSS-induced colitis, at least partly through maintaining the integrity of intestinal epithelial barrier, inhibiting apoptosis and inflammatory response.
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http://dx.doi.org/10.1016/j.ejphar.2021.173912DOI Listing
April 2021

β-patchoulene simultaneously ameliorated dextran sulfate sodium-induced colitis and secondary liver injury in mice via suppressing colonic leakage and flora imbalance.

Biochem Pharmacol 2020 12 2;182:114260. Epub 2020 Oct 2.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address:

Ulcerative colitis (UC) often occurs accompanied by colonic leakage and flora imbalance, resulting in secondary liver injury (SLI). SLI, in turn, aggravates UC, so the treatment of UC should not ignore it. β-patchoulene (β-PAE), a tricyclic sesquiterpene isolated from Pogostemon cablin, has been reported to exert a protective effect in gastrointestinal disease in our previous studies. However, its protection against UC and SLI remains unknown. Here we explored the protective effect and underlying mechanism of β-PAE against dextran sulfate sodium-induced UC and SLI in mice. The results indicated that β-PAE significantly reduced disease activity index, splenic index and attenuated the shortening of colonic length in UC mice. It alleviated colonic pathological changes and apoptosis through protecting tight junctions, reducing neutrophil aggregation, and inhibiting the release of pro-inflammatory cytokines and adhesion molecules. These effects of β-PAE were associated with the inhibition of TLR4/MyD88/NF-κB and ROCK1/MLC2 signalling pathway. UC-induced colonic leakage caused abnormally high LPS levels to result in SLI, and β-PAE markedly inhibited it. β-PAE simultaneously ameliorated SLI with reduced biomarker levels of endotoxin exposure and hepatic inflammation. High levels of LPS were also associated with flora imbalance in UC mice. However, β-PAE restored the diversity of gut microbiota and altered the relative abundance of characteristic flora of UC mice. Escherichia-dominated gut microbiota of UC mice was changed to Oscillospira-dominated after β-PAE treatment. In conclusion, pharmacological effects of β-PAE on UC and SLI were mainly contributed by suppressing colonic leakage and flora imbalance. The findings may have implications for UC treatment that not neglect the treatment of SLI.
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http://dx.doi.org/10.1016/j.bcp.2020.114260DOI Listing
December 2020

Patchouli alcohol protects against chronic unpredictable mild stress-induced depressant-like behavior through inhibiting excessive autophagy via activation of mTOR signaling pathway.

Biomed Pharmacother 2020 Jul 31;127:110115. Epub 2020 Mar 31.

Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China. Electronic address:

Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major chemical component of patchouli oil. This study investigated the antidepressant-like effect and mechanism of PA in chronic unpredictable mild stress (CUMS). Our results showed that PA markedly attenuated CUMS-induced depressant-like behaviors, including an effective increase of sucrose preference and spontaneous exploratory capacity, as well as reduction of immobility time. In addition, PA markedly attenuated CUMS-induced mTOR, p70S6K, and 4E-BP-1 phosphorylation reduction in the hippocampus. Furthermore, PA reversed CUMS-induced increases in LC3-II and p62 levels and CUMS-induced decrease in PSD-95 and SYN-I levels. These results indicated that the antidepressant-like effect of PA was correlated with the activation of the mTOR signaling pathway. Moreover, behavioral experimental results showed that the antidepressant-like effect of PA was blocked by rapamycin (autophagy inducer and mTOR inhibitor) and chloroquine (autophagic flux inhibitor). These results suggest that PA exerted antidepressant-like effect in CUMS rats through inhibiting autophagy, repairing synapse, and restoring autophagic flux in the hippocampus by activating the mTOR signaling pathway. The results render PA a promising antidepressant agent worthy of further development into a pharmaceutical drug for the treatment of depression.
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http://dx.doi.org/10.1016/j.biopha.2020.110115DOI Listing
July 2020

Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway.

Pharmacol Res 2020 02 19;152:104603. Epub 2019 Dec 19.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, PR China. Electronic address:

Berberine (BBR), a naturally-occurring isoquinoline alkaloid isolated from several Chinese herbal medicines, has been widely used for the treatment of dysentery and colitis. However, its blood concentration was less than 1 %, and intestinal microflora-mediated metabolites of BBR were considered to be the important material basis for the bioactivities of BBR. Here, we investigated the anti-colitis activity and potential mechanism of oxyberberine (OBB), a novel gut microbiota metabolite of BBR, in DSS-induced colitis mice. Balb/C mice treated with 3 % DSS in drinking water to induce acute colitis were orally administrated with OBB once daily for 8 days. Clinical symptoms were analyzed, and biological samples were collected for microscopic, immune-inflammation, intestinal barrier function, and gut microbiota analysis. Results showed that OBB significantly attenuated DSS-induced clinical manifestations, colon shortening and histological injury in the mice with colitis, which achieved similar therapeutic effect to azathioprine (AZA) and was superior to BBR. Furthermore, OBB remarkably ameliorated colonic inflammatory response and intestinal epithelial barrier dysfunction. OBB appreciably inhibited TLR4-MyD88-NF-κB signaling pathway through down-regulating the protein expressions of TLR4 and MyD88, inhibiting the phosphorylation of IκBα, and the translocation of NF-κB p65 from cytoplasm to nucleus. Moreover, OBB markedly modulated the gut dysbiosis induced by DSS and restored the dysbacteria to normal level. Taken together, the result for the first time revealed that OBB effectively improved DSS-induced experimental colitis, at least partly through maintaining the colonic integrity, inhibiting inflammation response, and modulating gut microflora profile.
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http://dx.doi.org/10.1016/j.phrs.2019.104603DOI Listing
February 2020

Patchouli Essential Oil and Its Derived Compounds Revealed Prebiotic-Like Effects in C57BL/6J Mice.

Front Pharmacol 2019 17;10:1229. Epub 2019 Oct 17.

State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.

(Blanco) Benth (PC) is a Chinese medicinal plant traditionally used for the treatment of gastrointestinal symptoms. To investigate the prebiotic effect of patchouli essential oil (PEO) and its derived compounds through the modulation of gut microbiota (GM). C57BL/6J mice were treated with the PEO and three active components of PEO, patchouli alcohol (PA), pogostone (PO) and β-patchoulene (β-PAE) for 15 consecutive days. Fecal samples and mucosa were collected for GM biomarkers studies. PEO, PA, PO, and β-PAE improve the gut epithelial barrier by altering the status of E-cadherin vs. N-cadherin expressions, and increasing the mucosal p-lysozyme and Muc 2. Moreover, the treatments also facilitate the polarization of M1 to M2 macrophage phenotypes, meanwhile, suppress the pro-inflammatory cytokines. Fecal microbial DNAs were analyzed and evaluated for GM composition by ERIC-PCR and 16S rRNA amplicon sequencing. The GM diversity was increased with the treated groups compared to the control. Further analysis showed that some known short chain fatty acids (SCFAs)-producing bacteria, , , , , and were significantly enriched in the treated groups. In addition, the key SCFAs receptors, GPR 41, 43 and 109a, were significantly stimulated in the gut epithelial layer of the treated mice. By contract, the relative abundance of pathogens spp., , and spp. were distinctly reduced by the treatments with PEO and β-PAE. Our findings provide insightful information that the microbiota/host dynamic interaction may play a key role for the pharmacological activities of PEO, PA, PO, and β-PAE.
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http://dx.doi.org/10.3389/fphar.2019.01229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812344PMC
October 2019

Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats.

Front Pharmacol 2019 1;10:1134. Epub 2019 Oct 1.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of (Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.
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http://dx.doi.org/10.3389/fphar.2019.01134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779828PMC
October 2019

T cell inhibition by pogostone from Pogostemon cablin (Blanco) Benth: In vitro and in vivo immunosuppressive analysis.

Mol Med Rep 2017 Oct 2;16(4):4511-4520. Epub 2017 Aug 2.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.

Various plant-derived compounds exhibit immunosuppressive activity in pre‑clinical investigations, suggesting that they may serve as natural alternatives for the prevention of inflammatory disorders and autoimmune diseases. The aim of the current study was to explore the immunosuppressive potential of pogostone (PO) derived from Pogostemon cablin (Blanco) Benth. Carboxyfluorescein diacetate succinimidyl ester‑labeled cell tracking demonstrated that PO (20‑80 µM) inhibited Concanavalin A (ConA)‑stimulated lymphocyte proliferation, which was mediated by G0/G1 phase arrest and accompanied by significant decreases in the expression of CD69 (early‑stage activation marker) and CD25 (mid‑stage activation marker) in T cells, as indicated by flow cytometry analysis. Furthermore, the proliferation blocking ability of PO (5‑80 µM) was not associated with cytotoxicity in normal lymphocytes or apoptosis in ConA‑stimulated lymphocytes. The inflammatory cytokine profile determination using a cytometric beads assay revealed that PO inhibited release of anti‑inflammatory interleukin (IL)‑10 and pro‑inflammatory IL‑6 from the stimulated lymphocytes. Furthermore, PO (10, 20 or 40 mg/kg) ameliorated the T‑cell mediated delayed type hypersensitivity response in Balb/c mice by reducing leukocyte infiltration and tissue edema, providing a further validation of the direct immunosuppressive activity of PO. Together, the present data suggest that PO would suppress T cell response via a direct non‑cytotoxic inactivation at the early stage, accompanied by regulation of the inflammatory cytokine profile, which highlights clinical implications for treatment of immune-based disorders.
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http://dx.doi.org/10.3892/mmr.2017.7147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5647011PMC
October 2017

Transformation of patchouli alcohol to β-patchoulene by gastric juice: β-patchoulene is more effective in preventing ethanol-induced gastric injury.

Sci Rep 2017 07 17;7(1):5591. Epub 2017 Jul 17.

Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.

Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.
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http://dx.doi.org/10.1038/s41598-017-05996-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514077PMC
July 2017

Investigation of Inclusion Complex of Patchouli Alcohol with β-Cyclodextrin.

PLoS One 2017 17;12(1):e0169578. Epub 2017 Jan 17.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China.

The objective of this study was to improve the stability and water-solubility of patchouli alcohol by complexing with β-cyclodextrin (β-CD). The interactions between patchouli alcohol and β-CD were characterized by differential scanning calorimetry (DSC), Fourier transformation-infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), and Scanning electron microscope (SEM), respectively. According to molecular modeling method, the enthalpy formation of host-guest illustrated the predominant configuration and the lowest value ΔbGo was -10.8174±1.9235 kcal/mol, suggesting the complex could reduce the energy of the system. The characterization analysis confirmed the formation of PA-CD inclusion complex, and the results indicated the advantage of the inclusion complex in stability and dissolution rates. These results identified PA-CD inclusion complex an effective way for the storage of PA, and better inclusion method still needed to be studied.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0169578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240955PMC
August 2017

Chongcao-Shencha Attenuates Liver and Kidney Injury through Attenuating Oxidative Stress and Inflammatory Response in D-Galactose-Treated Mice.

Evid Based Complement Alternat Med 2016 2;2016:3878740. Epub 2016 Jun 2.

The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.

The Chongcao-Shencha (CCSC), a Chinese herbal compound formula, has been widely used as food material and medicine for enhancing physical strength. The present study investigated the possible effect of CCSC in alleviating the liver and kidney injury in D-galactose- (D-gal-) treated mice and the underlying mechanism. Mice were given a subcutaneous injection of D-gal (200 mg/kg) and orally administered CCSC (200, 400, and 800 mg/kg) daily for 8 weeks. Results indicated that CCSC increased the depressed body weight and organ index induced by D-gal, ameliorated the histological deterioration, and decreased the levels of ALT, AST, BUN, and CRE as compared with D-gal group. Furthermore, CCSC not only elevated the activities of antioxidant enzymes SOD, CAT, and GPx but also upregulated the mRNA expression of SOD1, CAT, and GPx1, while decreasing the MDA level in D-gal-treated mice. Results of western blotting analysis showed that CCSC significantly inhibited the upregulation of expression of nuclear factor kappa B (NF-κB) p65, p-p65, p-IκBα, COX2, and iNOS and inhibited the downregulation of IκBα protein expression caused by D-gal. This study demonstrated that CCSC could attenuate the liver and kidney injury in D-gal-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response.
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http://dx.doi.org/10.1155/2016/3878740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909911PMC
June 2016

Anti-inflammatory activity of β-patchoulene isolated from patchouli oil in mice.

Eur J Pharmacol 2016 Jun 14;781:229-38. Epub 2016 Apr 14.

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, People's Republic of China; Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou 510006, People's Republic of China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, People's Republic of China. Electronic address:

β-Patchoulene (β-PAE) is a tricyclic sesquiterpene isolated from the oil of Pogostemon cablin (patchouli oil), which has been widely used in traditional Chinese medicine for the treatment of inflammatory diseases. However, as one of the major principle of patchouli oil, the biological activity of β-PAE has not been explored so far. In the present study, the anti-inflammatory activity in vivo, and the underlying mechanism, of β-PAE was investigated on experimental mice models of acute inflammation, i.e. xylene-induced ear edema, acetic acid-induced vascular permeability and carrageenan-induced paw edema. The results showed that β-PAE evoked a significant dose-dependent inhibition of ear edema induced by xylene, paw edema induced by carrageenan and suppressed the increase of vascular permeability elicited by acetic acid. Histopathological analysis indicated that β-PAE could markedly decrease the cellular infiltration in paw tissue. β-PAE was also shown to significantly decrease the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in edema paw. In addition, carrageenan-induced production of some pro-inflammatory cytokines: tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), prostaglandin E2 (PGE2) and nitric oxide (NO), were suppressed in a dose-dependent manner in mice subjected to β-PAE pretreatment, and it also significantly down-regulated the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Further analysis revealed that β-PAE also inhibited the translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus and stabilize the conversion of nuclear factor-κBα (IκBα) level. These results provided additional chemical and pharmacological basis for the traditional application of P. cablin in inflammatory disorders.
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http://dx.doi.org/10.1016/j.ejphar.2016.04.028DOI Listing
June 2016

Protective effects of patchouli alcohol isolated from on lipopolysaccharide-induced acute lung injury in mice.

Exp Ther Med 2016 Feb 8;11(2):674-682. Epub 2015 Dec 8.

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China.

Patchouli alcohol (PA) is a tricyclic sesquiterpene isolated from Pogostemon cablin, which exerts anti-inflammatory, anti-influenza and cognitive-enhancing bioactivities. The present study aimed to investigate the protective effects of PA on acute lung injury (ALI) induced by intratracheal instillation of lipopolysaccharide (LPS) in mice. Dexamethasone was used as a positive drug for protection against LPS-induced ALI. The results of the present study demonstrated that pretreatment with PA significantly increased survival rate, attenuated histopathologic damage and lung edema, and decreased the protein content in the bronchoalveolar lavage fluid (BALF) of mice with ALI. Furthermore, PA significantly inhibited the expression levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-6 in the BALF, downregulated the levels of myeloperoxidase and malondialdehyde, and upregulated the activity levels of superoxide dismutase and glutathione peroxidase in lung tissue. These results indicated that PA may exert potent protective effects against LPS-induced ALI in mice, the mechanisms of which are possibly associated with the anti-inflammatory and antioxidative activities of PA.
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http://dx.doi.org/10.3892/etm.2015.2918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4733951PMC
February 2016

Enhanced anti-tumor activity and reduced toxicity by combination andrographolide and bleomycin in ascitic tumor-bearing mice.

Eur J Pharmacol 2016 Apr 10;776:52-63. Epub 2016 Feb 10.

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China. Electronic address:

Bleomycin (BLM) is an effective anti-carcinogen. With the main detrimental effects of inducing pulmonary fibrosis on patients, its clinical use is limited. Developing agents that enhance the efficacy and attenuate the side effects of cancer chemotherapy are critical. Andrographolide (Andro), an active diterpenoid labdane component extracted from Andrographis panicula, is generally prescribed for treatment of inflammatory associated diseases. The study showed that BLM combined with Andro was significantly more effective than BLM alone on inhibiting the tumor growth, arresting the cell cycle at G0/G1 phase, promoting the capase-3 and capase-8 activity to induce cancer cell apoptosis. The underlying mechanisms may be related to the transcriptional regulation of P53/P21/Cyclin pathways. Moreover, BLM induced pulmonary fibrosis in tumor-bearing mice, but BLM combined with Andro dramatically alleviated the lesion in pulmonary fibrosis by activating the SOD, suppressing MDA and HYP production, in the meanwhile attenuating the IL-1β, TNF- α, IL-6 and TGF-β1 level. These mechanisms were associated with its effect on inhibition of protein expression of TGF-β, α-SMA, p-Smad2/3, enhanced expression of Smad7. Thus, it demonstrated that Andro might be a potential adjuvant therapeutic agent for BLM.
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http://dx.doi.org/10.1016/j.ejphar.2016.02.032DOI Listing
April 2016

Comparison of Helicobacter pylori Urease Inhibition by Rhizoma Coptidis, Cortex Phellodendri and Berberine: Mechanisms of Interaction with the Sulfhydryl Group.

Planta Med 2016 Mar 15;82(4):305-11. Epub 2015 Dec 15.

Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China.

Rhizoma Coptidis, Cortex Phellodendri, and berberine were reported to inhibit Helicobacter pylori. However, the underlying mechanism remained elusive. Urease plays a vital role in H. pylori colonization and virulence. In this work, aqueous extracts of Rhizoma Coptidis, Cortex Phellodendri of different origins, and purified berberine were investigated against H. pylori urease and jack bean urease to elucidate the inhibitory capacity, kinetics, and mechanism. Results showed that berberine was the major chemical component in Rhizoma Coptidis and Cortex Phellodendri, and the content of berberine in Rhizoma Coptidis was higher than in Cortex Phellodendri. The IC50 values of Rhizoma Coptidis were significantly lower than those Cortex Phellodendri and purified berberine, of which Coptis chinensis was shown to be the most active concentration- and time-dependent urease inhibitor. The Lineweaver-Burk plot analysis indicated that the inhibition pattern of C. chinensis against urease was noncompetitive for both H. pylori urease and jack bean urease. Thiol protectors (L-cysteine, glutathione, and dithiothreithol) significantly protected urease from the loss of enzymatic activity, while fluoride and boric acid showed weaker protection, indicating the active-site sulfhydryl group was possibly responsible for its inhibition. Furthermore, the urease inhibition proved to be reversible since C. chinensis-blocked urease could be reactivated by glutathione. The results suggested that the anti-urease activity of Rhizoma Coptidis was superior to that of Cortex Phellodendri and berberine, which was believed to be more likely to correlate to the content of total alkaloids rather than berberine monomer. The concentration- and time-dependent, reversible, and noncompetitive inhibition against urease by C. chinensis might be attributed to its interaction with the sulfhydryl group of the active site of urease.
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http://dx.doi.org/10.1055/s-0035-1558229DOI Listing
March 2016

Characterisation of the metabolism of pogostone in vitro and in vivo using liquid chromatography with mass spectrometry.

Phytochem Anal 2014 Mar-Apr;25(2):97-105

Introduction: Pogostone possesses potent anti-bacterial and anti-fungal activities and has been used for the quality control of essential oil of Pogostemon cablin. Pogostone is easily absorbed after oral administration but its metabolism in mammals remains elusive.

Objective: To investigate the metabolic profile of pogostone in vitro and in vivo.

Methods: High-performance liquid chromatography coupled with mass spectrometry (LC–MS) techniques were employed. Orbitrap MS and ion trap tandem mass spectrometry (MS/MS) were utilised to analyse the metabolism of pogostone by virtue of the high sensitivity and high selectivity in the measurement. In vitro experiment was carried out using rat liver microsomes while the in vivo study was conducted on rats, which were orally administered with pogostone (80 mg/kg).

Results: In total, three mono-hydroxylated, one di-hydroxylated, one mono-oxygenated, one di-oxygenated metabolite, one hydrolysis and one hydroxy conjugated metabolites were found. In addition hydroxylation was demonstrated to be a major metabolic pathway of pogostone.

Conclusion: LC–MS was demonstrated to be a powerful tool for the metabolite identification of pogostone. The tentative identification of metabolites provides an insight for the metabolic clues of pogostone.
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http://dx.doi.org/10.1002/pca.2471DOI Listing
September 2014

LC-MS/MS determination of pogostone in rat plasma and its application in pharmacokinetic studies.

Biomed Chromatogr 2013 Sep 18;27(9):1092-9. Epub 2013 Mar 18.

College of Chinese Medicines, Guangzhou University of Chinese Medicine, Guangzhou, PR China.

Pogostone is an important constituent of Pogostemon cablin (Blanco) Benth., and possesses various known bioactivities. A rapid, simple and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of pogostone in rat plasma using chrysophanol as internal standard (IS). The analytes were extracted with methanol and separated using a reversed-phase YMC-UltraHT Pro C18 column. Elution was achieved with a mobile phase consisting of methanol-water (75:25, v/v) for 5 min at a flow rate of 400 μL/min. The precursor/product transitions (m/z) under MS/MS detection with negative electrospray ionization (ESI) were 223.0 → 139.0 and 253.1 → 224.9 for pogostone and IS, respectively. The calibration curve was linear over the concentration range 0.05-160 µg/mL (r = 0.9996). The intra- and inter-day accuracy and precision were within ±10%. The validated method was successfully applied to the preclinical pharmacokinetic investigation of pogostone in rats after intravenous (5, 10 and 20 mg/kg) and oral administration (5, 10 and 20 mg/kg). Finally, the oral absolute bioavailability of pogostone in rats was calculated to be 70.39, 78.18 and 83.99% for 5, 10 and 20 mg/kg, respectively.
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http://dx.doi.org/10.1002/bmc.2897DOI Listing
September 2013
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