Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model

Sun, Na; Zhang, Hua; Sun, Panpan; Khan, Abad; Guo, Jianhua; Zheng, Xiaozhong; Sun, Yaogui; Fan, Kuohai; Li, Hongquan

doi:10.1016/j.phymed.2020.153289

Cited by 39 publications

(29 citation statements)

References 31 publications

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“…Matrine with 98.7% purity was purchased from National Institutes for Food and Drug Control (lot number:110805-201709). The maximum safe concentration (MSC) used in this experiment was 40 mg/kg [11]. Osthole with 98.0% purity was purchased from Nanjing Zelang Biotechnology Co., Ltd, China (Lot number:ZL20171212SCZS).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the combined dose was considered to be safe for KM mice. Ribavirin with 99.0% purity, the positive control drug, was purchased from Beijing Solarbio Technology Co., Ltd, China (CAS: 36791-04-5), the MSC used in this experiment was 40 mg/kg [11].…”

Section: Discussionmentioning

confidence: 99%

“…Matrine is an alkaloids and the main bioactive component of sophora. It has anti-in ammatory [9], anti-cancer [10], anti-virus [11,12], anti-apoptosis [13,14], and other biological activities. Osthole is the main bioactive ingredient of Fructus Cnidii and has anti-in ammatory [15], anti-cancer [16], anti-virus [17], anti-immunosuppression [18] and anti-apoptosis effects [19].…”

Section: Introductionmentioning

confidence: 99%

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Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

Wan

Sun

et al. 2021

Preprint

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Background PCV2 (Porcine circovirus type 2) is one of the major pathogens commonly in pigs, which can cause immunosuppression and apoptosis. Vaccinations and single drugs are not totally prevent and treat PCV2 diseases. We have previously reported that the synergistic anti-PCV2 effects of Matrine and Osthole were better than Matrine or Osthole alone in vitro, Matrine and Osthole were purchased with a clear content, chemical structure and plant origin. This study aimes to evaluate theirs synergistic anti-PCV2 effect and mechanism in Kunming (KM) mice model infected with PCV2. KM mice were randomly divided into 8 groups, namly: normal control group, PCV2 infected group, Matrine combined with Osthole high dose treatment group (40 mg/kg + 12 mg/kg), medium dose treatment group (20 mg/kg + 6 mg/kg), low dose treatment group (10 mg/kg + 3 mg/kg), Matrine treatment group (40 mg/kg), Osthole treatment group (12 mg/kg) and Ribavirin positive control group (40 mg/kg). PCV2 was intraperitoneally (i.p.) injected in all mice except the normal control group. At 5 days post-infection (dpi), mice in different treatment groups were injected i.p. with various doses of Matrine, Osthole and Ribavirin once daily for 5 consecutive days. Results The synergistic inhibition effect of Matrine and Osthole on PCV2 replication in mouse liver was significantly stronger than that of Matrine and Osthole alone. The protein expression of GRP78, p-PERK, p-eIF2α, ATF4, CHOP, cleaved caspase-3 and Bax were significantly reduced, but the protein expression of Bcl-2 was significantly increased in Matrine combined with Osthole groups, which alleviated the pathological change caused by PCV2, such as interstitial pneumonia, loss of spleen lymphocytes, infiltration of macrophages and eosinophils. Conclusions The synergistic effect of anti-apoptosis was better than that of Matrine and Osthole alone, although both of Matrine and Osthole could also directly inhibited the expression of PCV2 Cap and then inhibited the apoptosis of spleen cells induced by PCV2 Cap through the PERK pathway activated by endoplasmic reticulum (ER) GRP78. These results provide a new insight into controlling PCV2 infection and provide good component prescription candidate for the development of novel anti-PCV2 drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

Wan

Sun

et al. 2021

Preprint

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“…Matrine 30 is also considered a promising candidate as an immunosuppressive drug due to inhibiting autoimmune response in experimental models of multiple sclerosis [48,49]. It also exerts antiviral activity [50,51]. Extract isolated from the seeds of Sophora alopecuroides matrine 30, sophocarpine 31 and sophoramine 32 (Figure 10), with contents, respectively, of 32.85%, 26.55%, and 6.91%, have alleviated morphine withdrawal in patients [52].…”

Section: 6-naphthyridine Derivativesmentioning

confidence: 99%

Biological Activity of Naturally Derived Naphthyridines

2021

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Marine and terrestrial environments are rich sources of various bioactive substances, which have been used by humans since prehistoric times. Nowadays, due to advances in chemical sciences, new substances are still discovered, and their chemical structures and biological properties are constantly explored. Drugs obtained from natural sources are used commonly in medicine, particularly in cancer and infectious diseases treatment. Naphthyridines, isolated mainly from marine organisms and terrestrial plants, represent prominent examples of naturally derived agents. They are a class of heterocyclic compounds containing a fused system of two pyridine rings, possessing six isomers depending on the nitrogen atom’s location. In this review, biological activity of naphthyridines obtained from various natural sources was summarized. According to previous studies, the naphthyridine alkaloids displayed multiple activities, i.a., antiinfectious, anticancer, neurological, psychotropic, affecting cardiovascular system, and immune response. Their wide range of activity makes them a fascinating object of research with prospects for use in therapeutic purposes.

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“…It also alleviated the damage to organs and decreased the copy number of the PCV2 gene. Further investigation showed that matrine enhances phagocytosis by peritoneal macrophages and increases lymphocyte proliferation [ 63 ]. Oxymatrine ( Figure 8 ), the natural oxidized form of matrine, possesses strong immunomodulatory properties.…”

Section: Fighting Viruses By Modulating Immunitymentioning

confidence: 99%

Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products

Zhang

Xiong

Song

et al. 2021

Viruses

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Developing broad-spectrum antiviral drugs remains an important issue as viral infections continue to threaten public health. Host-directed therapy is a method that focuses on potential targets in host cells or the body, instead of viral proteins. Its antiviral effects are achieved by disturbing the life cycles of pathogens or modulating immunity. In this review, we focus on the development of broad-spectrum antiviral drugs that enhance the immune response. Some natural products present antiviral effects mediated by enhancing immunity, and their structures and mechanisms are summarized here. Natural products with immunomodulatory effects are also discussed, although their antiviral effects remain unknown. Given the power of immunity and the feasibility of host-directed therapy, we argue that both of these categories of natural products provide clues that may be beneficial for the discovery of broad-spectrum antiviral drugs.

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Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model

Cited by 39 publications

References 31 publications

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

Matrine combined with Osthole inhibited the PERK apoptosis of splenic lymphocytes in PCV2-infected mice model

Biological Activity of Naturally Derived Naphthyridines

Development of Broad-Spectrum Antiviral Agents—Inspiration from Immunomodulatory Natural Products

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