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. 2021 Jan 21;6(4):2462-2472.
doi: 10.1021/acsomega.0c02261. eCollection 2021 Feb 2.

Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Affiliations

Govaniadine Ameliorates Oxidative Stress, Inflammation, and Kupffer Cell Activation in Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Azra Jahan et al. ACS Omega. .

Abstract

Liver diseases such as hepatic carcinoma are one of the main health problems worldwide. Herbal drugs are largely used to treat liver injury in the indigenous system of medicine and may provide lead compounds for hepatoprotective drug discovery. The present study is investigated to test the Corydalis govaniana Wall. extract, fraction, and isolate therapeutically active constituents to explore their hepatoprotective, anti-inflammatory, and antioxidant activities. For this purpose, the antioxidant activity of govaniadine, caseadine, caseamine, and protopine was performed by assessing the scavenging events of the stable 2,2-diphenyl-1-picrylhydrazyl. Hepatoprotection of govaniadine was assessed in terms of reduction in serum enzymes (alanine aminotransferase, aspartate transaminase, and alkaline phosphatase) caused by CCl4-induced liver injury in rats and by histopathological techniques. All the compounds showed significant antioxidant activity with a percentage inhibition of 92.2, 86.7, 85.3, and 79.7, respectively, compared to propyl gallate 90.3%. Treatment with govaniadine reduced the serum enzyme level down to normal levels in the CCl4-treated group while inhibiting the increase of malondialdehyde, and the induction of superoxide dismutase and the glutathione level was upregulated. Histopathology showed ∼47% damage to the liver cells in the CCl4-treated group; reduction in this damaged area was found to be better upon using govaniadine. Immunohistochemistry results showed that govaniadine as compared to silymarin has exceedingly decreased the inflammation by halting the CCl4-induced activation of hepatic macrophages. In carrageenan-induced paw edema assay, govaniadine significantly alleviated the edema after 1-5 h at a dose of 20 mg/kg (26.00 and 28.5%), 50 mg/kg (22.05 and 27.0%), and 100 mg/kg (20.02 and 25.30%), respectively. The results of our experiments suggest that govaniadine showed antioxidant and hepatoprotective activity in liver injury. The hepatoprotective function of govaniadine may be associated to the scavenging of the free radical and attenuation of oxidative stress as well as inflammatory responses in the liver. Hence, govaniadine may be a lead compound for the hepatoprotective drug discovery process and further research is needed to find out their molecular mechanism of protection.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Hepatoprotective activity of alkaloids from C. govaniana. Histopathology of liver showing normal (green arrows) central vein, hepatic cords, and sinusoids in the untreated normal control (normal, A,B); pale necrotic areas (red arrows) after CCl4 treatment in the control group (CCl4, C,D); protection by the positive control 100 mg/kg silymarin (CCl4 + silymarin. E,F); protection by govaniadine (CCl4 + govaniadine. G,H) at a dose of 100 mg/kg. Caseadine (100 mg/kg)-treated liver showing some normal (green arrows) and a little injured (red arrows) hepatocytes around the central vein (CCl4 + caseadine. I,J); in caseamine-treated group necrotic areas are evident (100 mg/kg) after CCl4 treatment (CCl4 + caseamine. C,D); however, more injury was noticed in the group treated with protopine (CCl4 + protopine, M,N). Govaniadine protection is remarkably better than that of silymarin. Images were acquired at 10×, scale bar 200 μm, and for 20×, 100 μm scale bar.
Figure 2
Figure 2
Quantification of the effects of C. govaniana alkaloids on CCl4-induced hepatic injury: (A) serum ALT, AST, and ALP levels as markers of hepatic injury under various conditions. Note that the govaniadine indicated complete protection against CCl4-induced hepatic injury as compared to CCl4 (**P < 0.001) or CCl4+ silymarin (**P < 0.001). Caseadine has appreciably reduced the ALP, AST, and ALT levels up to some extent (**P < 0.001), even better than silymarin. Caseamine and protopine have shown some activities but still have shown an elevated level of ALT compared to their counterpart. (B) Percent damage of the liver as evaluated by histology under various conditions. Note that CCl4 damaged 47% area around the central vein, while 10% damage was seen in the silymarin group; however, govaniadine significantly revealed only 3.5% (**P < 0.001), which were completely absent with higher doses. Similarly caseadine, caseamine, and protopine significantly (**P < 0.001) reduced the damage down to 10, 13, and 19% respectively, as shown in (B).
Figure 3
Figure 3
Effects of C. govaniana alkaloids on the hepatic oxidative system. MDA (A), GSH (B), and SOD (C) in CCl4-intoxicated rats. Data were expressed as the mean ± SD, n = 10. ++P < 0.01, compared to the normal control; *P < 0.05, **P < 0.01, when compared to the CCl4 model group. Group I: normal control; group II: CCl4 model group; group III: 100 mg/kg silymarin + CCl4; group IV: 100 mg/kg govaniadine + CCl4; group V: 100 mg/kg caseadine + CCl4; group VI: 100 mg/kg caseamine + CCl4; group VII: protopine + CCl4.
Figure 4
Figure 4
Effects of alkaloids from C. govaniana on carragenine-induced paw edema. The swelling of paw was observed at 1–5 h after carragenine injection, respectively. The normal control group (a), the carragenine group (b), 20 mg/kg govaniadine + carragenine group (c), 50 mg/kg govaniadine + carragenine group (d), and 100 mg/kg govaniadine + carragenine group (e).
Figure 5
Figure 5
Effects of govaniadine on Kupffer cells. Immunohistochemistry for Kupffer cells of liver showed normal central vein (A) and hepatocyte nucleus stained with DAPI (B) with clear localization at sinusoidal spaces (C) of the normal control (A,B,C) group and increased migration of Kupffer cells (D) at the site of injury caused by CCl4 treatment (D,E,F). Silymarin treatment (G,H,I) reduced the activation of Kupffer cells to some extent (G). Normal distribution of Kupffer cells treated with 100 mg kg–1 govaniadine (J,K,L). DAPI (nucleus) is characterized by blue color. Magnification 40× and scale bar is 25 μm.
Figure 6
Figure 6
Structure of isolated alkaloid compounds from C. govaniana (1) govaniadine, (2) caseadine, (3) caseamine, (4) protopine.

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References

    1. Wolf P. L. Biochemical diagnosis of liver disease. Indian J. Clin. Biochem. 1999, 14, 59–90. 10.1007/bf02869152. - DOI - PMC - PubMed
    1. Alter M. J. Epidemiology of viral hepatitis and HIV co-infection. J. Hepatol. 2006, 44, S6.10.1016/j.jhep.2005.11.004. - DOI - PubMed
    1. Ghabril M.; Chalasani N.; Björnsson E. Drug-induced liver injury: a clinical update. Curr. Opin. Gastroenterol. 2010, 26, 222.10.1097/mog.0b013e3283383c7c. - DOI - PMC - PubMed
    1. Rechnagel R. O.; Glende E. A.; Plaa G. L. Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. Crit. Rev. Toxicol. 1973, 2, 263–297. 10.3109/10408447309082019. - DOI - PubMed
    1. Zhu R.-Z.; Xiang D.; Xie C.; Li J.-J.; Hu J.-J.; He H.-L.; Yuan Y.-S.; Gao J.; Han W.; Yu Y. Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice. World J. Gastroenterol. 2010, 16, 2771–2779. 10.3748/wjg.v16.i22.2771. - DOI - PMC - PubMed

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