**Zingerone [4-(3-Methoxy-4-hydroxyphenyl)-butan-2] Attenuates Lipopolysaccharide-Induced Inflammation and Protects Rats from Sepsis Associated Multi Organ Damage**

#### **Adil Farooq Wali 1,\*, Muneeb U Rehman 2, Mohammad Raish 3, Mohsin Kazi 3, Padma G. M. Rao 4, Osamah Alnemer 3, Parvaiz Ahmad 5 and Ajaz Ahmad 2,\***


Academic Editors: Ra ffaele Pezzani and Sara Vitalini Received: 19 October 2020; Accepted: 1 November 2020; Published: 4 November 2020

**Abstract:** The present investigation aimed to evaluate the protective effect of Zingerone (ZIN) against lipopolysaccharide-induced oxidative stress, DNA damage, and cytokine storm in rats. For survival study the rats were divided into four groups (n = 10). The control group was treated with normal saline; Group II received an intraperitoneal (i.p) injection (10 mg/kg) of LPS as disease control. Rats in Group III were treated with ZIN 150 mg/kg (p.o) 2 h before LPS challenge and rats in Group IV were given ZIN only. Survival of the rats was monitored up to 96 h post LPS treatment. In another set, the animals were divided into four groups of six rats. Animals in Group I served as normal control and were treated with normal saline. Animals in Group II were treated with lipopolysaccharide (LPS) and served as disease control. Group III animals were treated with ZIN 2 h before LPS challenge. Group IV served as positive control and were treated with ZIN (150 mg/kg orally). The blood samples were collected and used for the analysis of biochemical parameters like alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), blood urea nitrogen (BUN), Cr, Urea, lactate dehydrogenase (LDH), albumin, bilirubin (BIL), and total protein. Oxidative stress markers malondialdehyde (MDA), glutathione peroxidase (GSH), myeloperoxidase (MPO), and (DNA damage marker) 8-OHdG levels were measured in different organs. Level of nitric oxide (NO) and inflammatory markers like TNFα, IL-1ß, IL-1 α, IL-2, IL-6, and IL-10 were also quantified in plasma. Procalcitonin (PCT), a sepsis biomarker, was also measured. ZIN treatment had shown significant (*p* < 0.5) restoration of plasma enzymes, antioxidant markers and attenuated plasma proinflammatory cytokines and sepsis biomarker (PCT), thereby preventing the multi-organ and tissue damage in LPS-induced rats also confirmed by histopathological studies of different organs. The protective effect of ZIN may be due to its potent antioxidant potential. Thus ZIN can prevent LPS-induced oxidative stress as well as inflammatory and multi-organ damage in rats when administered to the LPS treated animals.

**Keywords:** zingerone; lipopolysaccharide; inflammation; anti-oxidant; cytokine storm; procalcitonin; histopathology
