PMID: 

J Pharm Pharmacol. 2017 Feb ;69(2):109-122. Epub 2016 Dec 1. PMID: 27905101

Abstract Title: 

A review on antiviral activity of the Himalayan medicinal plants traditionally used to treat bronchitis and related symptoms.

Abstract: 

OBJECTIVES: Bronchitis is a common respiratory tract infection of humans mainly caused by influenza virus, rhinovirus, adenovirus, coronavirus and respiratory syncytial virus. The aim of this review was to gather fragmented literature on ethnomedicinal plants used against bronchitis in the Himalayan region and their in-vitro validation against bronchitis causing viral pathogens.KEY FINDINGS: Present review contains ethnomedicines of total 55 plants from different countries of the Himalayas. Most of the literature reported was from India followed by Pakistan, China and Nepal. Familiarly used plant families for bronchitis treatment in the Himalayan region were Leguminosae (six plants) and Lamiaceae (five plants). Leaves and roots were the most common parts used in ethnomedicines against bronchitis. Of these 55 plants, only six plants have been studied in vitro against viral pathogens causing bronchitis. Different compounds like monoterpenoids, flavonoids, triterpenoids, iridoid glycosides, sesquiterpenes, benzoic and phenolic compounds were reportedly isolated from these plant extracts having strong antiviral potential.SUMMARY: The Himalayan regions possess variety of ethnomedicinal plants used against respiratory diseases, but still there are only few studies related with their in-vitro validation. We invite the attention of researchers for detailed ethnopharmacological and phytochemical studies on unexplored plants used to treat bronchitis for the development of novel antiviral drugs.

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PMID: 

J Nat Prod. 2017 02 24 ;80(2):298-307. Epub 2017 Feb 3. PMID: 28156114

Abstract Title: 

Sesquiterpenoids with Various Carbocyclic Skeletons from the Flowers of Chrysanthemum indicum.

Abstract: 

A phytochemical investigation of the flowers of Chrysanthemum indicum yielded sesquiterpenoids 1-25 with various carbocyclic skeletons, including 10 new (1-10) and 15 known (11-25) analogues. The structures were elucidated via their physical data, while the absolute configuration of compounds 6, 8, and 10 was assessed via electronic circular dichroism analysis. The evaluation of the effect of sesquiterpenoids on porcine epidemic diarrhea virus (PEDV) replication showed that compounds 1-5, 12, 14, 16, 17, 19, and 21 increased cell viability against cell death in PEDV-injected cells. Compounds 2, 12, and 17 were selected and investigated for their inhibition of proteins required for PEDV replication. Compounds 2 and 17 significantly reduced PEDV nucleocapsid and spike protein synthesis compared with azauridin as a positive control.

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PMID: 

Arch Virol. 2017 Jun ;162(6):1467-1476. Epub 2017 Feb 7. PMID: 28175983

Abstract Title: 

Glycyrrhizin inhibits porcine epidemic diarrhea virus infection and attenuates the proinflammatory responses by inhibition of high mobility group box-1 protein.

Abstract: 

Porcine epidemic diarrhea (PED), caused by porcine epidemic diarrhea virus (PEDV) infection, leads to significant economic losses in the swine industry worldwide. In our studies, we found that glycyrrhizin, the major component of licorice root extracts, could moderately inhibit PEDV infection in Vero cells, when analyzed by western blot, qRT-PCR and a plaque formation assay. We also revealed that glycyrrhizin inhibited the entry and replication of PEDV. In addition, we demonstrated that glycyrrhizin decreased the mRNA levels of proinflammatory cytokines. Since glycyrrhizin is a competitive inhibitor of high mobility group box-1 (HMGB1), we confirmed that TLR4 and RAGE (£ associated with PEDV pathogenesis during the infection in Vero cells. In summary, our studies provide a molecular basis for developing novel therapeutic methods to control PEDV infection, based on glycyrrhizin and its derivatives.

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PMID: 

Amino Acids. 2017 Dec ;49(12):1931-1943. Epub 2017 Mar 3. PMID: 28258325

Abstract Title: 

N-Acetylcysteine supplementation alleviates intestinal injury in piglets infected by porcine epidemic diarrhea virus.

Abstract: 

Porcine epidemic diarrhea virus (PEDV) infects the intestine of young pigs, but effective measures for prevention and treatment are lacking. N-Acetylcysteine (NAC) has been shown to reduce endotoxin-induced intestinal dysfunction. This study was conducted with the PEDV-infected neonatal piglet model to determine the effect of NAC supplementation on intestinal function. Thirty-two 7-day-old piglets were randomly allocated to one of four treatments in a 2 × 2 factorial design consisting of two liquid diets (0 or 50 mg/kg BW NAC supplementation) and oral administration of 0 or 10TCID(50% tissue culture infectious dose) PEDV. On day 7 of the trial, half of the pigs (n = 8) in each dietary treatment received either sterile saline or PEDV (Yunnan province strain) solution at 10TCIDper pig. On day 10 of the trial, D-xylose (0.1 g/kg BW) was orally administrated to all pigs. One hour later, jugular vein blood samples were collected, and then all pigs were killed to obtain the small intestine. PEDV infection increased diarrhea incidence, while reducing ADG. PEDV infection also decreased plasma D-xylose concentration, smallintestinal villus height, mucosal I-FABP and villin mRNA levels but increased mucosal MX1 and GCNT3 mRNA levels (P 

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PMID: 

Evid Based Complement Alternat Med. 2019 ;2019:8306519. Epub 2019 Nov 19. PMID: 31827564

Abstract Title: 

Effect ofExtract toward Incised Wound Healing Process in Mice () Clinically and Histologically.

Abstract: 

Wound healing entails a sequence of complex biological processes, which is a protective function of the body that focuses on a quick recovery. Reducing wound healing time is crucial in a wound as it lowers the chance of infection and decreases complications and costs. Papaya extract was obtained by a maceration method. It contains papain enzyme, flavonoid, saponin, and alkaloid, which act as an anti-inflammatory, astringent substance, vasodilator, antioxidant, analgesic, with antifungal, and antibacterial properties, and increase the collagen synthesis. This study aimed to assess the effect ofextract application toward incised wound healing process in mice () clinically and histologically. This experimental laboratory study was performed using 24 mice weighing between 30 and 40 grams and 12 and 14 weeks of age as experimental animals. Each group was incised along 5 mm at the labial gingiva under both of mandible anterior teeth with a depth reaching alveolar bone. Papaya extract was applied topically in the morning and evening for 14 days. The clinical result was obtained by assessing the length of wound closure measured every day for 14 days. Based on the statistic test result, it showed that the papaya extract has a significant effect (≤ 0.05) toward the healing process of an incised oral wound in mice. Histologically at day 14, 75% concentration papaya extract showed perfect epithelial layer and fibrillation.

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PMID: 

Bioorg Med Chem Lett. 2017 07 1 ;27(13):3019-3025. Epub 2017 May 8. PMID: 28527823

Abstract Title: 

Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut).

Abstract: 

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high fatality of piglets, influencing the swine industry. Japanese horse chestnut (seed of Aesculus turbinata) contains many saponin mixtures, called escins, and has been used for a long time as a traditional medicinal plant. Structure-activity relationship (SAR) studies on escins have revealed that acylations at C-21 and C-22 with angeloyl or tigloyl groups were important for their cytotoxic effects. However, the strong cytotoxicity of escins makes them hard to utilize for other diseases and to develop as nutraceuticals. In this research, we investigated whether escin derivatives 1-7 (including new compounds 2, 3, 5 and 6), without the angeloyl or tigloyl groups and with modified glycosidic linkages by hydrolysis, have PEDV inhibitory effects with less cytotoxicity. Compounds 1-7 had no cytotoxicity at 20μM on VERO cells, while compounds 8-10 showed strong cytotoxicity at similar concentrations on PEDV. Our results suggest that escin derivatives showed strong inhibitory activities on PEDV replication with lowered cytotoxicity. These studies propose a method to utilize Japanese horse chestnut for treating PEDV and to increase the diversity of its bioactive compounds.

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PMID: 

Microb Pathog. 2018 Jan ;114:124-128. Epub 2017 Nov 21. PMID: 29170045

Abstract Title: 

Astragalus polysaccharides inhibit avian infectious bronchitis virus infection by regulating viral replication.

Abstract: 

The avian coronavirus causes infectious bronchitis (IB), which is one of the most serious diseases affecting the avian industry worldwide. However, there are no effective strategies for controlling the IB virus (IBV) at present. Therefore, development of novel antiviral treatment strategies is urgently required. As reported, astragalus polysaccharides (APS) have potential antiviral effects against several viruses; however, the antiviral effect of APS against IBV remains unclear. In this study, we explored whether APS had the potential to inhibit IBV infectionby utilizing several in vitro experimental approaches. To this end, the effect of APS on the replication of IBV was examined in chicken embryo kidney (CEK) cells. Viral titers were calculated by using the plaque formation assay, and the cytotoxicity of APS was tested by utilizing a Cell Counting Kit-8 assay. The expression of viral mRNA and cytokine (IL-1β, IL-6, IL-8 and TNF-α) mRNA transcripts was determined by real-time quantitative RT-PCR(qRT-PCR). IBV titers in infected CEK cells treated with APS were significantly reduced in a dose-dependent manner, indicating that APS inhibited IBV replication in vitro. We also found that the decreased viral replication after APS treatment was associated with reduced mRNA levels of the cytokines IL-1B, IL-6, IL-8 and TNF-α. In conclusion, these results suggest that APS exhibit antiviral activities against IBV and it may represent a potential therapeutic agent for inhibiting the replication of IBV.

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PMID: 

Ann Transl Med. 2019 Dec ;7(24):811. PMID: 32042827

Abstract Title: 

The protective effect ofpolysaccharide on mice with depression by inhibiting NLRP3 inflammasome.

Abstract: 

Background: Depression is associated with the abnormal activation of the human inflammatory response system, which is a life-threatening disorder affecting millions of people of all ages around the world. The purposes of the present study were to examine the effect ofpolysaccharide (LJP), a polysaccharide extracted fromThunb., on depressed mice treated with the unpredictable emotional stress stimulation.Methods: The components of LJP after extraction were detected by HPLC. Depression model is established through chronic unpredictable stimulation, and the depression behavior was assessed by mouse behavioral assessment, including open field, elevated plus maze, tail suspension, forced swim. Pathological changes in hippocampus of mice were observed by HE and toluidine blue staining. Protein expression of NLRP3 inflammasome pathway was detected by WB.Results: It was showed that LJP mainly consisted of 8.7% GalA, 8.2% Rha, 16.2% Gal, 19.5% Ara, 26.9% Glc and 20.5% Man, with the average molecular weight approximately ranging from 1 to 1,000 kDa, which could significantly reduce the time in the open arms and the immobility time of the depressed mice in behavioral tests, and the expressions of NLRP3, IL-1β, and caspase-1 in the hippocampus of depressed mice were significantly upregulated.Conclusions: LJP exhibited a strong protective effect on mice with depression by inhibiting NLRP3 inflammasome. The results will help to understand the potential use of Lonicera japonica Thun polysaccharide in pharmaceutical and food applications better.

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PMID: 

J Sci Food Agric. 2019 Jan 30 ;99(2):703-710. Epub 2018 Aug 13. PMID: 29971802

Abstract Title: 

Dietary inclusion of mushroom (Flammulina velutipes) stem waste on growth performance and immune responses in growing layer hens.

Abstract: 

BACKGROUND: Medicinal mushrooms contain biologically active substances that can be used as an immune-modulating agent in poultry. The present study aimed to investigate the effects of Flammulina velutipes mushroom waste (FVW) on performance, immune response and serum immunity in growing layer hens.RESULTS: No significant differences (P>0.05) were observed with respect to average daily feed intake, body weight gain and feed conversion ratio among the experimental groups during the entire study period (1-70 days). Antibody titers against Newcastle disease and infectious bronchitis were higher (P

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PMID: 

Bioorg Med Chem. 2019 05 15 ;27(10):1981-1989. Epub 2019 Mar 26. PMID: 30940566

Abstract Title: 

Identification and design of novel small molecule inhibitors against MERS-CoV papain-like protease via high-throughput screening and molecular modeling.

Abstract: 

The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PL), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the ICvalue of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.

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