Tarasuk Mayuri, Songprakhon Pucharee, Chimma Pattamawan, Sratongno Panudda, Na-Bangchang Kesara, Yenchitsomanus Pa-Thai
Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Virus Res. 2017 Aug 15;240:180-189. doi: 10.1016/j.virusres.2017.08.011. Epub 2017 Aug 31.
Since severe dengue virus (DENV) infection in humans associates with both high viral load and massive cytokine production - referred to as "cytokine storm", an ideal drug for treatment of DENV infection should efficiently inhibit both virus production and cytokine expression. In searching for such an ideal drug, we discovered that α-mangostin (α-MG), a major bioactive compound purified from the pericarp of the mangosteen fruit (Garcinia mangostana Linn), which has been used in traditional medicine for several conditions including trauma, diarrhea, wound infection, pain, fever, and convulsion, inhibits both DENV production in cultured hepatocellular carcinoma HepG2 and Huh-7 cells, and cytokine/chemokine expression in HepG2 cells. α-MG could also efficiently inhibit all four serotypes of DENV. Treatment of DENV-infected cells with α-MG (20μM) significantly reduced the infection rates of four DENV serotypes by 47-55%. α-MG completely inhibited production of DENV-1 and DENV-3, and markedly reduced production of DENV-2 and DENV-4 by 100 folds. Furthermore, it could markedly reduce cytokine (IL-6 and TNF-α) and chemokine (RANTES, MIP-1β, and IP-10) transcription. These actions of α-MG are more potent than those of antiviral agent (ribavirin) and anti-inflammatory drug (dexamethasone). Thus, α-MG is potential to be further developed as therapeutic agent for DENV infection.
由于人类严重登革病毒（DENV）感染与高病毒载量和大量细胞因子产生相关，即所谓的“细胞因子风暴”，因此治疗DENV感染的理想药物应能有效抑制病毒产生和细胞因子表达。在寻找这种理想药物的过程中，我们发现α-山竹黄酮（α-MG），一种从山竹果（莽吉柿）果皮中纯化得到的主要生物活性化合物，在传统医学中已用于治疗多种病症，包括创伤、腹泻、伤口感染、疼痛、发热和惊厥，它既能抑制培养的肝癌HepG2和Huh-7细胞中的DENV产生，又能抑制HepG2细胞中的细胞因子/趋化因子表达。α-MG还能有效抑制DENV的所有四种血清型。用α-MG（20μM）处理DENV感染的细胞可使四种DENV血清型的感染率显著降低47%-55%。α-MG完全抑制了DENV-1和DENV-3的产生，并使DENV-2和DENV-4的产生显著降低了100倍。此外，它还能显著降低细胞因子（IL-6和TNF-α）和趋化因子（RANTES、MIP-1β和IP-10）转录。α-MG的这些作用比抗病毒药物（利巴韦林）和抗炎药物（地塞米松）更强。因此，α-MG有潜力进一步开发成为治疗DENV感染的药物。
