PMID: 

J Evid Based Complementary Altern Med. 2017 Jan ;22(1):166-174. Epub 2016 Apr 6. PMID: 27055821

Abstract Title: 

Prevention and Treatment of Influenza, Influenza-Like Illness, and Common Cold by Herbal, Complementary, and Natural Therapies.

Abstract: 

In recent years viral respiratory tract infections, especially influenza viruses, have had a major impact on communities worldwide as a result of unavailability of effective treatment or vaccine. The frequent alterations in the antigenic structures of respiratory viruses, particularly for RNA viruses, pose difficulties in production of effective vaccines. The unavailability of optimal medication and shortage of effective vaccines suggests the requirement for alternative natural therapies. Several herbal remedies were used for prevention and treatment viral respiratory illnesses. Among those that were found effective included maoto, licorice roots, antiwei, North American ginseng, berries, Echinacea, plants extracted carnosic acid, pomegranate, guava tea, and Bai Shao. There is scientific evidence regarding the effectiveness of several complementary therapies for colds. Oral zinc may reduce the length and severity of a cold. Taking vitamin C supplements on a regular basis only slightly reduces the length and severity of colds. Probiotics were found better than placebo in reducing the number episodes of acute upper respiratory tract infections, the rate of episodes of acute upper respiratory tract infection and reducing antibiotic use. Alkaline diets or drinks might have antiviral properties as in vitro studies demonstrated inactivation effect of alkaline medium on respiratory virus. Earthing might have a natural anti-inflammatory effect for human body. It is now accepted that an overwhelming inflammatory response is the cause of human deaths from avian H5N1 influenza infection. Earthing accelerates immune response following vaccination, as demonstrated by increases of gamma globulin concentration. No in vivo or clinical studies were found that investigate the role of alkalization or earthing on respiratory viral infections. Thus, future studies are recommended to reveal any potential curative effects.

read more

PMID: 

Life Sci. 2020 Jan 22:117351. Epub 2020 Jan 22. PMID: 31981629

Abstract Title: 

Zinc promotes functional recovery after spinal cord injury by activating Nrf2/HO-1 defense pathway and inhibiting inflammation of NLRP3 in nerve cells.

Abstract: 

AIMS: To study the specific therapeutic effect of zinc on spinal cord injury (SCI) and its specific protective mechanism.MAIN METHODS: The effects of zinc ions on neuronal cells were examined in a mouse SCI model and in vitro. In vivo, neurological function was assessed by Basso Mouse Scaleat (BMS) at 1, 3, 5, 7, 10, 14, 21, and 28 days after spinal cord injury. The number of neurons and histomorphology were observed by nissl staining and hematoxylin-eosin staining (HE). The chromatin and mitochondrial structure of neurons were detected by transmission electron microscopy (TEM). The expression of nuclear factor erythroid 2related factor 2 (Nrf2)-related antioxidant protein and nlrp3 inflammation-related protein were detected in vivo and in vitro by western blot (WB) and immunofluorescence (IF), respectively.KEY FINDINGS: Zinc treatment promoted motor function recovery on days 3, 5, 7, 14, 21 and 28 after SCI. In addition, zinc reduces the mitochondrial void rate in spinal neuronal cells and promotes neuronal recovery. At the same time, zinc reduced the levels of reactive oxygen species (ROS) and malondialdehyde in spinal cord tissue after SCI, while increasing superoxide dismutase activity and glutathione peroxidase production. Zinc treatment resulted in up-regulation of nrf2/ho-1 levels and down-regulation of nlrp3 inflammation-associated protein expression in vitro and in vivo.SIGNIFICANCE: Zinc has a protective effect on spinal cord injury by inhibiting oxidative damage and nlrp3 inflammation. Potential mechanisms may include activation of the Nrf 2/Ho-1 pathway to inhibit nlrp3 inflammation following spinal cord injury. Zinc has the potential to treat SCI.

read more

PMID: 

Brain Behav Immun. 2020 Jan 29. Epub 2020 Jan 29. PMID: 32006614

Abstract Title: 

Zinc, but not paracetamol, prevents depressive-like behavior and sickness behavior, and inhibits interferon-gamma and astrogliosis in rats.

Abstract: 

Considering all mental and addictive disorders, depression is the most responsible for years of life lost due to premature mortality and disability. Antidepressant drugs have limited effectiveness. Depression can be triggered by immune/inflammatory factors. Zinc and paracetamol interfere with immune system and have demonstrated beneficial effects on depression treatment when administered concomitant with antidepressant drugs. The objective of this study was to test zinc and/or paracetamol as treatments of depressive-like behavior, sickness behavior, and anxiety in rats, as well as to understand the central and peripheral mechanisms involved. Sickness behavior and depressive-like behavior were induced in rats with repetitive lipopolysaccharide (LPS, 1 mg/kg for two consecutive days) administrations. Rats received zinc and/or paracetamol for three consecutive days. Sickness behavior (daily body weight and open field general activity); anxiety (light-dark test); depressive-like/antidepressant behavior (forced swim test); plasma corticosterone and interferon (IFN)-gamma levels; and glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) brain expression were evaluated. LPS induced sickness behavior and depressive-like behavior, as well as elevated IFN-gamma levels and increased GFAP expression. Zinc prevented both behavioral and biochemical impairments. Paracetamol and zinc+paracetamol association induced only slight beneficial effects. Anxiety, corticosterone, and TH do not seem be related with depression and the other behavioral and neuroimmune changes. In conclusion, zinc treatment was beneficial for sickness behavior and depressive-like behavior without concomitant administration of antidepressants. IFN-gamma and GFAP were linked with the expression of sickness behavior and depressive-like behavior and were also involved with the antidepressant effects. Therefore, zinc, IFN-gamma, and GFAP pathways should be considered for depression treatment.

read more

PMID: 

BMC Complement Altern Med. 2019 Feb 1 ;19(1):38. Epub 2019 Feb 1. PMID: 30709346

Abstract Title: 

2-Ethoxystypandrone, a novel small-molecule STAT3 signaling inhibitor from Polygonum cuspidatum, inhibits cell growth and induces apoptosis of HCC cells and HCC Cancer stem cells.

Abstract: 

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is an oncogene constitutively activated in hepatocellular carcinoma (HCC) cells and HCC cancer stem cells (CSCs). Constitutively activated STAT3 plays a pivotal role in holding cancer stemness of HCC CSCs, which are essential for hepatoma initiation, relapse, metastasis and drug resistance. Therefore, STAT3 has been validated as a novel anti-cancer drug target and the strategies targeting HCC CSCs may bring new hopes to HCC therapy. This study aimed to isolate and identify small-molecule STAT3 signaling inhibitors targeting CSCs from the ethyl acetate (EtOAc) extract of the roots of Polygonum cuspidatum and to evaluate their in vitro anti-cancer activities.METHODS: The chemical components of the EtOAc extract and the subfractions of P. cuspidatum were isolated by using various column chromatographies on silical gel, Sephadex LH-20, and preparative HPLC. Their chemical structures were then determined on the basis of spectroscopic data including NMR, MS and IR analysis and their physicochemical properties. The inhibitory effects of the isolated compounds against STAT3 signaling were screened by a STAT3-dependent luciferase reporter gene assay. The tyrosine phosphorylation of STAT3 was examined by Western Blot analysis. In vitro anti-cancer effects of the STAT3 pathway inhibitor were further evaluated on cell growth of human HCC cells by a MTT assay, on self-renewal capacity of HCC CSCs by the tumorsphere formation assay, and on cell cycle and apoptosis by flow cytometry analysis, respectively.RESULTS: The EtOAc extract of the roots of P. cuspidatum was investigated and a novel juglone analogue 2-ethoxystypandrone (1) along with seven known compounds (2-8) was isolated. Among the eight isolated compounds 1-8, 2-ethoxystypandrone was a novel and potent STAT3 signaling inhibitor (IC = 7.75 ± 0.18 μM), and inhibited the IL-6-induced and constitutive activation of phosphorylation of STAT3 in HCC cells. Moreover, 2-ethoxystypandrone inhibited cell survival of HCC cells (IC = 3.69 ± 0.51 μM ~ 20.36 ± 2.90 μM), blocked the tumorspheres formation (IC = 2.70 ± 0.28 μM), and induced apoptosis of HCC CSCs in a dose-dependent manner.CONCLUSION: A novel juglone analogue 2-ethoxystypandrone was identified from the EtOAc extract of the roots of P. cuspidatum and was demonstrated to be a potent small-molecule STAT3 signaling inhibitor, which strongly blocked STAT3 activation, inhibited proliferation, and induced cell apoptosis of HCC cells and HCC CSCs. 2-Ethoxystypandrone as a STAT3 signaling inhibitor might be a promising lead compound for further development into an anti-CSCs drug.

read more

PMID: 

Zhongguo Zhong Yao Za Zhi. 2019 Feb ;44(3):546-552. PMID: 30989921

Abstract Title: 

[Effect of ethanolic extract of Polygonum cuspidatum on acute gouty arthritis in mice through NLRP3/ASC/caspase-1 axis].

Abstract: 

The aim of this paper was to study the effect and mechanism of alcohol extract from Polygonum cuspidatum(PCE) on acute gouty arthritis in C57 BL/6 mice through NLRP3/ASC/caspase-1 axis. The model mice which injected with ankle joint injection of sodium urate crystals(MSU) were orally administrated with three different concentration of PCE, with colchicine as positive control. HE staining was used for observing the morphological changes of synovial tissue; concentration of IL-1β, IL-6 and TNF-α secreted by synovial tissue of the ankle joint were detected by ELISA; mRNA and protein expression of NLRP3, ASC and caspase-1 in synovial tissue were detected by RT-PCR and Western blot respectively. The results showed that the swelling degree of ankle joint in model mice were significantly elevated; expression of IL-1β, IL-6 and TNF-α were significantly increased; mRNA and protein expression of NLRP3, ASC and caspase-1 also significant increase, compared with normal control group. The swelling degree of ankle joint significantly relief; expression of IL-1β, IL-6 and TNF-α in joint synovium significantly decrease; mRNA and protein expression of NLRP3, ASC and caspase-1 were significantly decrease in PCE treatment group compared with model group. Our research implied that alcohol extract from P. cuspidatum had positive effect on acute gouty arthritis in mice, andthe regulation of NLRP3/ASC/caspase-1 axis may be its mechanism.

read more

PMID: 

Food Sci Nutr. 2019 Jun ;7(6):2006-2016. Epub 2019 May 1. PMID: 31289648

Abstract Title: 

Capability of polygonum cuspidatum extract in inhibiting AGEs and preventing diabetes.

Abstract: 

Diabetes is a metabolic disorder disease associated with advanced glycation end products (AGEs) and protein glycation. The effect of polygonum cuspidatum extract (PE) on AGEs and Nε-(Carboxymethyl)-L-lysine formation, protein glycation, and diabetes was investigated. Six primary phenolics in a range of 12.36 mg/g for ellagic acid to 0.01 mg/g for piceid were determined in PE. In an intermediate-moisture-foods model, inhibition rate of PE was as high as 54.2% for AGEs and 78.9% for CML under aw 0.75. The protein glycation was also inhibited by PE. In a diabetic rat model, the levels of blood glucose, serum malondialdehyde, cholesterol, triglycerides, and low-density lipoproteins were effectively reduced by PE treatment. The antioxidation capacity (T-AOC) and superoxide dismutase (SOD) activity were also mediated by PE. Additionally, the activates of liver function-related enzymes including alkaline phosphatase (ALP), glutamate pyruvate transaminase (GPT), and glutamate oxaloacetate transaminase (GOT) in diabetic rat were improved by PE.

read more

PMID: 

Phytomedicine. 2019 Oct ;63:152986. Epub 2019 Jun 10. PMID: 31310912

Abstract Title: 

Polygonum cuspidatum extract attenuates fructose-induced liver lipid accumulation through inhibiting Keap1 and activating Nrf2 antioxidant pathway.

Abstract: 

BACKGROUND: Polygonum cuspidatum has been used in traditional Chinese medicine to treat liver disorders associated with oxidative stress, inflammation and lipid accumulation for centuries in patients.PURPOSE: The aim of this study was to examine whether P. cuspidatum extract (PCE) prevented against fructose-induced liver lipid accumulation via regulating Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.METHOD: PCE was administered orally to male Sprague-Dawley rats given 10% fructose drinking water for 6 weeks at 80 and 160 mg/kg once daily for 11 weeks.RESULTS: PCE significantly alleviated liver lipid accumulation in fructose-fed rats with metabolic syndrome. It also inhibited Keap1, activated Nrf2 antioxidant pathway, resulting in the suppression of oxidative stress, evidenced by reducing hydrogen peroxide (HO), malondialdehyde (MDA) and hydroxy radical (OH) levels, and increasing glutathione (GSH)/oxidized glutathione (GSSG) ratio as well as superoxidase dismutase (SOD) and catalase (CAT) activity in the liver of fructose-fed rats. Additionally, PCE up-regulated peroxisome proliferator activated receptor-α (PPAR-α), and down-regulated sterol regulatory element binging protein 1 (SREBP-1), fatty acid synthetase (FAS) and stearoyl-CoA desaturase-1 (SCD-1) in this animal model, being consistent with its reduction of triglyceride (TG) levels.CONCLUSION: These results demonstrate that PCE reduces oxidative stress, and prevent lipid accumulation in the liver of fructose-fed rats possibly by targeting the Keap1/Nrf2 pathway. PCE may be a promising therapeutic strategy for fructose-associated liver lipid accumulation.

read more

PMID: 

J Microbiol Biotechnol. 2020 Jan 28 ;30(1):21-30. PMID: 31838799

Abstract Title: 

Antioxidant and Anti-Obesity Activities ofExtract through Alleviation of Lipid Accumulation on 3T3-L1 Adipocytes.

Abstract: 

Natural products are widely used due to their various biological activities which include antiinflammatory, antioxidant, and anti-obesity effects. In this study, we determined the antioxidative and anti-obesity effects of50% ethanol extract (PEE). The antioxidative effect of PEE was evaluated using its radical scavenging activity, total phenolic content, and reducing power. The anti-obesity effect of PEE was investigated using 3T3-L1 adipocytes. The antioxidative activity of PEE was progressively increased in various concentrations, mainly due to the presence of phenolic compounds. PEE also alleviated lipid accumulation on 3T3-L1 adipocytes and downregulated the mRNA and protein production of adipogenesis-related (SREBP-1c, PPARγ, C/EBPα) and lipogenesis-related (aP2, FAS, ACC) markers. Furthermore, we found that the inhibitory effect on lipid accumulation via PEE was caused by the alleviation of NF-κB, p38 MAPK, ERK1/2, and JNK at the protein level. Taken together, our results imply that PEE is a potential antioxidantthat can prevent obesityassociated disorders.

read more

PMID: 

Curr Drug Metab. 2013 May ;14(4):392-413. PMID: 23330927

Abstract Title: 

Polyphenols: a diverse class of multi-target anti-HIV-1 agents.

Abstract: 

Polyphenols are a versatile class of compounds that represent secondary metabolites from higher plants and which are abundantly present in the human diet. Epidemiological data suggest protective effects of polyhenols in relation to cancer, cardiovascular diseases, diabetes, infectious diseases and age-related conditions. HIV/AIDS remains prevalent in many parts of the world as acute infection and as anti-retroviral drug (ARV)-managed chronic disease. Due to the nature of the human immune deficiency virus (HIV) and an increased use of ARVs many drug-resistant HIV strains have emerged and continue to do so. This makes it impossible to rely on one standard drug treatment regime. This review summarizes anti- HIV activities of polyphenols. It highlights the diversity of modes of action by which polyphenols – according to their respective compound classes – exert their activities. Additionally, this review discusses polyphenols as multi-target anti-HIV agents and provides the context of in-vivo and clinical data. Based on the presented data, a three-pronged approach for further anti-HIV drug discovery is suggested applying methods of combinatorial medicinal chemistry on the diverse and sometimes unique scaffolds of polyphenols. The latter being selected according to the approach of 'reverse pharmacology' as a creative way to place safety and other clinical consideration at the beginning of the drug discovery- and development process.

read more

PMID: 

Viruses. 2018 08 30 ;10(9). Epub 2018 Aug 30. PMID: 30200234

Abstract Title: 

Virucidal and Synergistic Activity of Polyphenol-Rich Extracts of Seaweeds against Measles Virus.

Abstract: 

Although preventable by vaccination, Measles still causes thousands of deaths among young children worldwide. The discovery of new antivirals is a good approach to control new outbreaks that cause such death. In this study, we tested the antiviral activity against Measles virus (MeV) of Polyphenol-rich extracts (PPs) coming from five seaweeds collected and cultivated in Mexico. An MTT assay was performed to determine cytotoxicity effect, and antiviral activity was measured by syncytia reduction assay and confirmed by qPCR. PPs from(formerly, Phaeophyceae) and(Rhodophyta) showed the highest Selectivity Index (SI),>3750 and>576.9 respectively. Both PPs extracts were selected to the subsequent experiments owing to their high efficacy and low cytotoxicity compared with ribavirin (SI of 11.57). The combinational effect of PPs with sulphated polysaccharides (SPs) and ribavirin were calculated by using Compusyn software. Synergistic activity was observed by combining both PPs with low concentrations ofSPs (0.01µg/mL). The antiviral activity of the best combinations was confirmed by qPCR. Virucidal assay, time of addition, and viral penetration evaluations suggested that PPs act mainly by inactivating the viral particle. To our knowledge, this is the first report of the virucidal effect of Polyphenol-richextracts of seaweeds.

read more