Publications by authors named "Zuqing Su"

16 Publications

  • Page 1 of 1

Phytochemicals: Targeting Mitophagy to Treat Metabolic Disorders.

Front Cell Dev Biol 2021 3;9:686820. Epub 2021 Aug 3.

Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Metabolic disorders include metabolic syndrome, obesity, type 2 diabetes mellitus, non-alcoholic fatty liver disease and cardiovascular diseases. Due to unhealthy lifestyles such as high-calorie diet, sedentary and physical inactivity, the prevalence of metabolic disorders poses a huge challenge to global human health, which is the leading cause of global human death. Mitochondrion is the major site of adenosine triphosphate synthesis, fatty acid β-oxidation and ROS production. Accumulating evidence suggests that mitochondrial dysfunction-related oxidative stress and inflammation is involved in the development of metabolic disorders. Mitophagy, a catabolic process, selectively degrades damaged or superfluous mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial function. It is considered to be one of the major mechanisms responsible for mitochondrial quality control. Growing evidence shows that mitophagy can prevent and treat metabolic disorders through suppressing mitochondrial dysfunction-induced oxidative stress and inflammation. In the past decade, in order to expand the range of pharmaceutical options, more and more phytochemicals have been proven to have therapeutic effects on metabolic disorders. Many of these phytochemicals have been proved to activate mitophagy to ameliorate metabolic disorders. Given the ongoing epidemic of metabolic disorders, it is of great significance to explore the contribution and underlying mechanisms of mitophagy in metabolic disorders, and to understand the effects and molecular mechanisms of phytochemicals on the treatment of metabolic disorders. Here, we investigate the mechanism of mitochondrial dysfunction in metabolic disorders and discuss the potential of targeting mitophagy with phytochemicals for the treatment of metabolic disorders, with a view to providing a direction for finding phytochemicals that target mitophagy to prevent or treat metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.686820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369426PMC
August 2021

Kun-Dan Decoction Ameliorates Insulin Resistance by Activating AMPK/mTOR-Mediated Autophagy in High-Fat Diet-Fed Rats.

Front Pharmacol 2021 28;12:670151. Epub 2021 May 28.

Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome. Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells. Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells. The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.670151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193673PMC
May 2021

Mitophagy in Hepatic Insulin Resistance: Therapeutic Potential and Concerns.

Front Pharmacol 2019 10;10:1193. Epub 2019 Oct 10.

Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China.

Metabolic syndrome, characterized by central obesity, hypertension, and hyperlipidemia, increases the morbidity and mortality of cardiovascular disease, type 2 diabetes, nonalcoholic fatty liver disease, and other metabolic diseases. It is well known that insulin resistance, especially hepatic insulin resistance, is a risk factor for metabolic syndrome. Current research has shown that hepatic fatty acid accumulation can cause hepatic insulin resistance through increased gluconeogenesis, lipogenesis, chronic inflammation, oxidative stress and endoplasmic reticulum stress, and impaired insulin signal pathway. Mitochondria are the major sites of fatty acid β-oxidation, which is the major degradation mechanism of fatty acids. Mitochondrial dysfunction has been shown to be involved in the development of hepatic fatty acid-induced hepatic insulin resistance. Mitochondrial autophagy (mitophagy), a catabolic process, selectively degrades damaged mitochondria to reverse mitochondrial dysfunction and preserve mitochondrial dynamics and function. Therefore, mitophagy can promote mitochondrial fatty acid oxidation to inhibit hepatic fatty acid accumulation and improve hepatic insulin resistance. Here, we review advances in our understanding of the relationship between mitophagy and hepatic insulin resistance. Additionally, we also highlight the potential value of mitophagy in the treatment of hepatic insulin resistance and metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.01193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6795753PMC
October 2019

Basil polysaccharide inhibits hypoxia-induced hepatocellular carcinoma metastasis and progression through suppression of HIF-1α-mediated epithelial-mesenchymal transition.

Int J Biol Macromol 2019 Sep 25;137:32-44. Epub 2019 Jun 25.

The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China. Electronic address:

Invasion and metastasis of cancerous cells affects the treatment and prognosis of hepatocellular carcinoma (HCC). HIF-1α-induced epithelial-mesenchymal transition (EMT) is a critical process associated with cancer metastasis. Basil polysaccharide (BPS), one of the major active ingredients isolated from Basil (Ocimum basilicum L.), has been identified to possess an antitumor activity for HCC. In our current study, BPS was obtained by water extraction and ethanol precipitation method and the characterization was analyzed through ultraviolet absorption spectra and Fourier-transform infrared spectrum. A CoCl-induced hypoxia model and a HCC cell line-derived xenograft (CDX) model were used to explore the anti-metastasis efficacy and the mechanism that underlies the antitumor activity of BPS. The results showed that hypoxia could facilitate EMT and promote HCC cells migration and/or invasion. Conversely, BPS inhibited the progression and metastasis of tumor, as well as reversed EMT by causing cytoskeletal remodeling under hypoxic conditions. Moreover, BPS alleviated tumor hypoxia by targeting HIF1α, and the mesenchymal markers (β-catenin, N-cadherin and vimentin) were down-regulated, while the epithelial markers (E-cadherin, VMP1 and ZO-1) were up-regulated after BPS treatment under hypoxic conditions. Thus, these results suggested that BPS may be a valuable option for use in clinical treatment of HCC and other malignant tumors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2019.06.189DOI Listing
September 2019

Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis.

J Cell Physiol 2019 04 14;234(4):3661-3674. Epub 2018 Sep 14.

Deparment of Pharmacology of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. However, the pathogenesis of psoriasis is multifactorial and is not fully understood. MicroRNAs (miRNAs) represent a promising class of small, noncoding RNA molecules that have a large impact on cellular functions by regulating gene expression. Here we reported that microRNA-187 (miR-187), which is one of the most dynamic microRNAs identified in the deep screening miRNAs profile, is downregulated in inflammatory cytokines-stimulated keratinocytes and psoriatic skins. By luciferase activity assay and gain-of-function studies, we showed that miR-187 inhibits keratinocytes hyperproliferation by targeting CD276. Moreover, overexpression of miR-187 decreases acanthosis and reduces the disease severity in psoriasis mouse models. Taken together, the results of our study implies miR-187 as a critical factor in psoriasis pathogenesis, which could be a potent target for psoriasis treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcp.27135DOI Listing
April 2019

Scutellarin induces apoptosis and autophagy in NSCLC cells through ERK1/2 and AKT Signaling Pathways in vitro and in vivo.

J Cancer 2018 7;9(18):3247-3256. Epub 2018 Sep 7.

Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510120, China.

Curative molecular therapy for non-small cell lung cancer (NSCLC) is still lacking. Scutellarin, an active flavone extracted from , displays anti-tumor property in diverse cancer types, yet its tumor-suppressive effect on NSCLC is not reported. In this study, we found that scutellarin significantly inhibited the proliferation of NSCLC cells, induced cell apoptosis, and triggered autophagy. Notably, inhibition of autophagy with inhibitor HCQ attenuated the anti-proliferative activity of scutellarin, indicating that scutellarin-induced autophagy is antineoplastic. In addition, HCQ treatment reduced scutellarin-induced apoptosis. Further study demonstrated that scutellarin stimulated phosphorylation of ERK1/2, and inhibition of ERK1/2 with inhibitor U0126 markedly attenuated scutellarin-induced autophagy. Similarly, scutellarin downregulated the expression of p-AKT, and AKT inhibitor MK-2206 induced autophagy. Moreover, there also existed crosstalk between ERK and AKT pathways. Finally, xenograft nude mice experiment proved that scutellarin treatment significantly reduced tumor growth and increased the levels of LC3-II and p-ERK1/2, suppressed p-AKT in mice tumors. Thus, our study for the first time uncovered the anti-cancer function of scutellarin on NSCLC cells, and might provide a potential novel therapy for treatment of patients with NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.25921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160677PMC
September 2018

Resveratrol combined with total flavones of hawthorn alleviate the endothelial cells injury after coronary bypass graft surgery.

Phytomedicine 2018 Feb 12;40:20-26. Epub 2018 Jan 12.

Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong 510006, China; The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address:

Objective: To explore the preventive and therapeutic effects of Resveratrol combined with total flavones of hawthorn, compatibility of traditional Chinese medicines, on the endothelial cells injury after artery bypass graft surgery.

Methods: The animal model of coronary artery bypass grafting (CABG) was prepared by transplanting a segment of autologous jugular vein onto the transected common carotid artery in rabbits. After CABG surgery, the rabbits were administrated with saline (model group), aspirin (Aspirin group), resveratrol (Res group), total flavones of hawthorn (Haw group) and resveratrol combined with total flavones of hawthorn (Res+Haw group) once a day for eight weeks, respectively. Eight weeks later, the grafting arteries from all group were obtained for the pathomorphism observation, peripheral blood was collected to detect circulating endothelial cells (CECs) by flow cytometry. And the concentration of albumen and mRNA of ICAM-1 in the serum were measured by western blot and quantitative real-time polymerase chain reaction, respectively.

Results: Compared with the model group, the level of CECs density and the expressions of albumen and mRNA of ICAM-1 were significantly decreased in the aspirin,resveratrol,total flavones of hawthorn and resveratrol combined with total flavones of hawthorn groups (P < .05). Of note, above all parameters were lower in Res group than aspirin group.

Conclusion: The Resveratrol combined with total flavones of hawthorn could protect the endothelial cells after coronary artery bypass graft.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phymed.2017.12.037DOI Listing
February 2018

Cryptotanshinone reduces psoriatic epidermal hyperplasia via inhibiting the activation of STAT3.

Exp Dermatol 2018 03;27(3):268-275

Department of Pharmacology of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The discovery of new therapeutic drugs with the efficacious and safe ability to prevent epidermal hyperplasia is extremely urgent for psoriasis. Cryptotanshinone (CTS), an active component isolated from the root of Salvia miltiorrhiza Bunge, has been reported to have antibacterial and antitumor effects. However, its effects on psoriasis have not been reported. Here, we investigated the therapeutic effects of CTS on imiquimod (IMQ)-induced psoriatic-like skin model and explored the underlying mechanisms. Our results revealed that CTS effectively alleviates IMQ-induced epidermal hyperplasia. In vitro studies also indicated that CTS potently inhibits the growth of keratinocytes. We further found that STAT3, a transcription factor for the cell growth, is the key mediator of CTS on the proliferation of keratinocytes. Taken together, our findings indicated that the curative effects of CTS on psoriasis are accomplished mainly through modulating STAT3, which providing evidences to develop CTS as a potential therapeutic agent for patients with psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/exd.13511DOI Listing
March 2018

Basil polysaccharide attenuates hepatocellular carcinoma metastasis in rat by suppressing H3K9me2 histone methylation under hepatic artery ligation-induced hypoxia.

Int J Biol Macromol 2018 Feb 16;107(Pt B):2171-2179. Epub 2017 Oct 16.

Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancers in the world. Tumor metastasis is an important factor of poor prognosis in patients with HCC. Tumor hypoxia can promote tumor cell metastasis in HCC. Epigenetic modification is closely related to tumor hypoxia and metastasis. In our previous research, we found that basil polysaccharide suppressed migration and invasion of HCC cell by inhibiting hypoxia induced histone methylation in vitro. In the present study, we investigated the effect of basil polysaccharide on the walker 256 carcinoma cell metastasis in rat. We established an intratumoral hypoxic model in rat by hepatic artery ligation (HAL). Then rats were treated with basil polysaccharide (75, 150 and 300mg/kg). The results showed that HAL could promote tumor metastasis by aggravating tumor hypoxia. However, basil polysaccharide could inhibit tumor metastasis in intratumoral hypoxia. Further, we demonstrated that basil polysaccharide could down-regulate the expression of HIF-1α, G9a, LSD1, JMJD1A, JMJD2B, JARID1B and H3K9me2. Synchronously, basil polysaccharide could increase E-cadherin and VMP1 expression, and decrease N-cadherin, vimentin and β-catenin expression. The results indicated that histone modifying enzymes might be a new therapeutic target of basil polysaccharide on hepatocellular carcinoma metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2017.10.088DOI Listing
February 2018

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/3878740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4909911PMC
June 2016

(-)-Patchouli alcohol protects against Helicobacter pylori urease-induced apoptosis, oxidative stress and inflammatory response in human gastric epithelial cells.

Int Immunopharmacol 2016 Jun 24;35:43-52. Epub 2016 Mar 24.

School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, PR China; Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan 523808, ,PR China. Electronic address:

(-)-Patchouli alcohol (PA), the major active principle of Pogostemonis Herba, has been reported to have anti-Helicobacter pylori and gastroprotective effects. In the present work, we aimed to investigate the possible protective effect of PA on H. pylori urease (HPU)-injured human gastric epithelial cells (GES-1) and to elucidate the underlying mechanisms of action. Results showed that pre-treatment with PA (5.0, 10.0, 20.0μM) was able to remarkably ameliorate the cytotoxicity induced by 17.0U/mg HPU in GES-1 cells. Flow cytometric analysis on cellular apoptosis showed that pre-treatment with PA effectively attenuated GES-1 cells from the HPU-induced apoptosis. Moreover, the cytoprotective effect of PA was found to be associated with amelioration of the HPU-induced disruption of MMP, attenuating oxidative stress by decreasing contents of intracellular ROS and MDA, and increasing superoxide dismutase (SOD) and catalase (CAT) enzymatic activities. In addition, pre-treatment with PA markedly attenuated the secretion of nitric oxide (NO) and pro-inflammatory cytokines such as interleukin-2 (IL-2), interleukin-4 (IL-4) and tumor necrosis factor-α (TNF-α), whereas elevated the anti-inflammatory cytokine interleukin-13 (IL-13) in the HPU-stimulated GES-1 cells. Molecular docking assay suggested that PA engaged in the active site of urease bearing nickel ions and interacted with important residues via covalent binding, thereby restricting the active urease catalysis conformation. Our experimental findings suggest that PA could inhibit the cellular processes critically involved in the pathogenesis of H. pylori infection, and its protective effects against the HPU-induced cytotoxicity in GES-1 cells are believed to be associated with its anti-apoptotic, antioxidative, anti-inflammatory and HPU inhibitory actions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2016.02.022DOI 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0035-1558229DOI Listing
March 2016

Protective effects of pogostone from Pogostemonis Herba against ethanol-induced gastric ulcer in rats.

Fitoterapia 2015 Jan 3;100:110-7. Epub 2014 Dec 3.

College of Chinese Medicines, Guangzhou University of Chinese Medicine, 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:

We examined the protective effect of pogostone (PO), a chemical constituent isolated from Pogostemonis Herba, on the ethanol-induced gastric ulcer in rats. Administration of PO at doses of 10, 20 and 40 mg/kg body weight prior to ethanol ingestion effectively protected the stomach from ulceration. The gastric lesions were significantly ameliorated by all doses of PO as compared to the vehicle group. Pre-treatment with PO prevented the oxidative damage and the decrease of prostaglandin E2 (PGE2) content. In addition, PO pretreatment markedly increased the mucosa levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), and decreased gastric malonaldehyde (MDA), relative to the vehicle group. In the mechanistic study, significant elevation of non-protein-sulfhydryl (NP-SH) was observed in the gastric mucosa pretreated by PO. Analysis of serum cytokines indicated that PO pretreatment obviously elevated the decrease of interleukin-10 (IL-10) level, while markedly mitigated the increment of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretions in ethanol-induced rats. Taken together, these results strongly indicate that PO could exert a gastro-protective effect against gastric ulceration, and the underlying mechanism might be associated with the stimulation of PGE2, improvement of antioxidant and anti-inflammatory status, as well as preservation of NP-SH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fitote.2014.11.017DOI Listing
January 2015

Kinetics and mechanism study of competitive inhibition of jack-bean urease by baicalin.

ScientificWorldJournal 2013 1;2013:879501. Epub 2013 Oct 1.

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

Baicalin (BA) is the principal component of Radix Scutellariae responsible for its pharmacological activity. In this study, kinetics and mechanism of inhibition by BA against jack-bean urease were investigated for its therapeutic potential. It was revealed that the IC₅₀ of BA against jack-bean urease was 2.74 ± 0.51 mM, which was proved to be a competitive and concentration-dependent inhibition with slow-binding progress curves. The rapid formation of initial BA-urease complex with an inhibition constant of K(i) = 3.89 × 10⁻³ mM was followed by a slow isomerization into the final complex with an overall inhibition constant of K(i)* = 1.47 × 10⁻⁴ mM. High effectiveness of thiol protectors against BA inhibition indicated that the strategic role of the active-site sulfhydryl group of the urease was involved in the blocking process. Moreover, the inhibition of BA was proved to be reversible due to the fact that urease could be reactivated by dithiothreitol but not reactant dilution. Molecular docking assay suggested that BA made contacts with the important activating sulfhydryl group Cys-592 residues and restricted the mobility of the active-site flap. Taken together, it could be deduced that BA was a competitive inhibitor targeting thiol groups of urease in a slow-binding manner both reversibly and concentration-dependently, serving as a promising urease inhibitor for treatments on urease-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/879501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807542PMC
June 2014
-->