Berberine inhibits cytosolic phospholipase A2 and protects against LPS-induced lung injury and lethality independent of the alpha2-adrenergic receptor in mice.
Acute lung injury is still a significant clinical problem having a high mortality rate despite significant advances in antimicrobial therapy and supportive care made in the past few years. Our previous study demonstrated that berberine (Ber) remarkably decreased mortality and attenuated the lung injury in mice challenged with LPS, but the mechanism behind this remains unclear. Here, we report that pretreatment with Ber significantly reduced pulmonary edema, neutrophil infiltration, and histopathological alterations; inhibited protein expression and phosphorylation of cytosolic phospholipase A2; and decreased thromboxane A2 release induced by LPS. Yohimbine, an alpha2-adrenergic receptor antagonist, did not antagonize these actions of Ber. Furthermore, pretreatment with Ber decreased TNF-alpha production and mortality in mice challenged with LPS, which were enhanced by yohimbine, and Ber combined with yohimbine also improved survival rate in mice subjected to cecal ligation and puncture. Taken together, these observations indicate that Ber attenuates LPS-induced lung injury by inhibiting TNF-alpha production and cytosolic phospholipase A2 expression and activation in an alpha2-adrenoceptor-independent manner. Berberine combined with yohimbine might provide an effective therapeutic approach to acute lung injury during sepsis.
Zhang
Hao-qing
HQ
Department of Pathophysiology, Medical College of Jinan University, Guangzhou, Guangdong, China.
Wang
Hua-dong
HD
Lu
Da-xiang
DX
Qi
Ren-bin
RB
Wang
Yan-ping
YP
Yan
Yu-xia
YX
Fu
Yong-mei
YM
D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D008070:Lipopolysaccharides / Q000378:metabolism*; D055370:Lung Injury; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D054510:Phospholipases A2, Cytosolic / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011654:Pulmonary Edema / Q000473:pathology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
D008070:Lipopolysaccharides; D018341:Receptors, Adrenergic, alpha-2; D014409:Tumor Necrosis Factor-alpha; D001599:Berberine; D015016:Yohimbine; D054510:Phospholipases A2, Cytosolic