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. 2020 Nov 4;25(21):5127.
doi: 10.3390/molecules25215127.

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 , Ajaz Ahmad  2
Affiliations

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

Adil Farooq Wali et al. Molecules. .

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 TNF-α, IL-1ß, IL-1α, 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: anti-oxidant; cytokine storm; histopathology; inflammation; lipopolysaccharide; procalcitonin; zingerone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structure of Zingerone [4-(3-methoxy-4-hydroxyphenyl)-butan-2-one].
Figure 2
Figure 2
Kaplan–Meier survival plot (n = 10 rats per group). Effect of zingerone (ZIN) 150 mg/kg on survival rate of LPS induce systemic inflammation in rats.
Figure 3
Figure 3
Effect of zingerone (ZIN) on LPS-induced DNA damage and oxidative stress marker. (A) 8-OHdG levels (ng/mL), (B) Nitric Oxide (NO) levels (µM). Results are represented as mean ± SEM of six rats/group. * p < 0.05 vs. control; # p < 0.05 vs. LPS group.
Figure 4
Figure 4
Effect of zingerone (ZIN) on LPS-induced oxidative stress as malondialdehyde (MDA) (nmol/kg). (A) Brain, (B) lung, (C) liver, and (D) kidney. Results are represented as mean ± SEM of six rats/group. * p < 0.05 vs. control; # p < 0.05 vs. LPS group.
Figure 5
Figure 5
Effect of zingerone (ZIN) on LPS-induced oxidative stress as GSH (µmol/kg). (A) Brain, (B) Lung, (C) Liver and (D) Kidney. Results are represented as mean ± SEM of six rats/group. * p < 0.05 vs. control; # p < 0.05 vs. LPS group.
Figure 6
Figure 6
Effect of zingerone (ZIN) on LPS-induced oxidative stress as MPO (U/g). (A) Brain, (B) lung, (C) liver, and (D) kidney. Results are represented as mean ± SEM of six rats/group. * p < 0.05 vs. control; # p < 0.05 vs. LPS group.
Figure 7
Figure 7
Effect of zingerone (ZIN) on LPS-induced Proinflammatory cytokines and sepsis biomarker PCT (pg/mL). (A) TNF-α, (B) IL-1α, (C) IL-2, (D) IL-6, (E) IL-8, (F) IL-10, and (G) procalcitonin (PCT). Results are represented as mean ± SEM of six rats/group. * p < 0.05 vs. control; # p < 0.05 vs. LPS group.
Figure 8
Figure 8
Light histograms of different rat organs (hematoxylin and eosin stains, magnification 40× and scale bar of 100 µm). Effect of ZIN in LPS intoxicated rats. Brain (A) normal control group: Showing normal histological structure with intact neurons, (B) LPS treated rats: Showing neuronal loss with condensed nuclei, (C) Rats treated with (ZIN 150 mg/kg + LPS: Showing decrease in neuronal loss with presence of intact neurons. Kidney (A) normal control group: Showing normal histological structure of the glomeruli and tubules at the cortex with absence of histopathological alterations, (B) LPS treated rats: Showing marked inflammatory cell aggregation in between the tubules, marked degeneration in the lining epithelium of all the tubules, and blood vessel congestion, (C) Rats treated with (ZIN 150 mg/kg + LPS: Showing absence of histopathological alterations. Liver (A) Normal control group: Showing normal histological structure of the central vein and intact hepatocytes, (B) LPS treated rats: Showing severe loss of hepatic architecture with multiple focal necrosis, ballooning degeneration in the hepatocytes, (C) Rats treated with ZIN 150 mg/kg + LPS: Showing absence of histopathological alterations. Lung (A) Normal control group showing normal morphology, (B) LPS treated rats: Showing moderate to severe hemorrhage, thickening of alveolar septa, emphysema, and infiltration of leukocytes in walls alveoli, (C) Rats treated with ZIN 150 mg/kg + LPS: Showing absence of histopathological changes.
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