New insights into the effects and mechanism of a classic traditional Chinese medicinal formula on influenza prevention.
BACKGROUND
KangBingDu (KBD) is a classic traditional Chinese medicinal formula widely used to treat influenza. However, little information is available from controlled studies regarding the anti-influenza pharmacological activities of KBD and its underlying mechanisms, at least partly due to the lack of appropriate study models.


OBJECTIVE
We hypothesized that KBD might provide a protection against influenza infection by reducing the host's susceptibility to viruses. To prove it, mouse restraint stress model was employed.


METHODS
Mice were restricted and infected with influenza virus. KBD (13 and 26mg/kg/d) was orally administrated to mice from the first day of restraint stress and lasted for 7 days (twice a day). Mice were monitored daily for morbidity, symptom severity, and mortality for 21 days. The histopathologic changes were examined. For the study of mechanisms of action, we investigated whether KBD could promote mitochondria antiviral signaling protein (MAVS)-mediated antiviral signal and inhibit nuclear factor-kappa B (NF-κB)-mediated inflammation response.


RESULTS
KBD significantly decreased the susceptibility of restraint mice to influenza virus, as evidenced by lowered mortality, attenuated inflammation and reduced viral replications in lungs. Further results revealed that KBD elevated the protein expression of MAVS, which subsequently increased the IFN-β and IFITM3 protein levels, thereby helping to fight viral infections. Finally, we identified that (R,S)-goitrin, mangiferin, forsythin and forsythoside A were effective components in KBD against influenza viral infections.


CONCLUSIONS
KBD can reduce the susceptibility to influenza virus via mitochondrial antiviral signaling.
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Huan
H
Chen
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Chong
C
Jie
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Lu-Ping
LP
Tang
Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China.
He
H
Meng
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Xiao-Bo
XB
Li
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Yan-Bing
YB
Li
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Le-Xing
LX
Chen
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Chang
C
Yan
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China.
Hiroshi
H
Kurihara
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China. Electronic address: liyifang706@jnu.edu.cn.
Yi-Fang
YF
Li
Anti-Stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China; Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China. Electronic address: rongronghe@jnu.edu.cn.
Rong-Rong
RR
He
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002681:China; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts
Influenza virus; KangBingDu (KBD); Restraint stress; Susceptibility; Traditional Chinese medicine