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Hepatoprotective effects of Aureobasidium pullulans derived Beta 1,3-1,6 biological response modifier glucans in a STAM- animal model of non-alcoholic steatohepatitis

Nobunao Ikewaki, Gene Kurosawa, Masaru Iwasaki, Senthilkumar Preethy, Vidyasagar Devaprasad Dedeepiya, Suryaprakash Vaddi, Rajappa Senthilkumar, Gary A Levy, View ORCID ProfileSamuel JK Abraham
doi: https://doi.org/10.1101/2021.07.08.451700
Nobunao Ikewaki
1Dept. of Medical Life Science, Kyushu University of Health and Welfare, Japan
2Institute of Immunology, Junsei Educational Institute, Nobeoka, Miyazaki, Japan
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Gene Kurosawa
3Department of Academic Research Support Promotion Facility, Center for Research Promotion and Support, Fujita Health University, Aichi, Japan
4MabGenesis KK, Nagoya, Japan
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Masaru Iwasaki
5Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan
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Senthilkumar Preethy
6Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
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Vidyasagar Devaprasad Dedeepiya
7Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
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Suryaprakash Vaddi
8Department of Urology, Yashoda Hospitals, Hyderabad, India
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Rajappa Senthilkumar
6Fujio-Eiji Academic Terrain (FEAT), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
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Gary A Levy
9Professor Emeritus, Medicine and Immunology, University of Toronto, Ontario, Canada
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Samuel JK Abraham
5Centre for Advancing Clinical Research (CACR), University of Yamanashi - School of Medicine, Chuo, Japan
7Mary-Yoshio Translational Hexagon (MYTH), Nichi-In Centre for Regenerative Medicine (NCRM), Chennai, India
10Antony-Xavier Interdisciplinary Scholastics (AXIS), GN Corporation Co. Ltd., Kofu, Japan
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  • ORCID record for Samuel JK Abraham
  • For correspondence: drsam@nichimail.jp drspp@nichimail.jp
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Abstract

Background Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Lifestyle disorders such as obesity, diabetes and dyslipidaemia predispose to and are associated with the disease progression. Conventional modalities are mainly symptomatic, with no definite solution. Beta glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study.

Methods In the STAM™ murine model of NASH, five groups were studied for eight weeks— (1) vehicle (RO water), (2) AFO-202 beta glucan; (3) N-163 beta glucan, (4) AFO-202+N-163 beta glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed.

Results AFO-202 beta glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta glucan decreased fibrosis and inflammation significantly (p value<0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups.

Conclusion This preclinical study supports the potential of N-163 and AFO-202 beta glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.

Figure

Competing Interest Statement

Author Samuel Abraham is a shareholder in GN Corporation, Japan which in turn is a shareholder in the manufacturing company of the Beta Glucans described in the study.

Footnotes

  • (nikewaki{at}phoenix.ac.jp), (gene{at}fujita-hu.ac.jp), (miwasaki{at}yamanashi.ac.jp), (drspp{at}nichimail.jp), (dedeepiya_76{at}yahoo.co.in), (suryaprakashuro{at}gmail.com), (rsk{at}nichimail.jp), (gary.levy{at}uhn.ca), (drsam{at}nichimail.jp)

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted July 09, 2021.
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Hepatoprotective effects of Aureobasidium pullulans derived Beta 1,3-1,6 biological response modifier glucans in a STAM- animal model of non-alcoholic steatohepatitis
Nobunao Ikewaki, Gene Kurosawa, Masaru Iwasaki, Senthilkumar Preethy, Vidyasagar Devaprasad Dedeepiya, Suryaprakash Vaddi, Rajappa Senthilkumar, Gary A Levy, Samuel JK Abraham
bioRxiv 2021.07.08.451700; doi: https://doi.org/10.1101/2021.07.08.451700
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Hepatoprotective effects of Aureobasidium pullulans derived Beta 1,3-1,6 biological response modifier glucans in a STAM- animal model of non-alcoholic steatohepatitis
Nobunao Ikewaki, Gene Kurosawa, Masaru Iwasaki, Senthilkumar Preethy, Vidyasagar Devaprasad Dedeepiya, Suryaprakash Vaddi, Rajappa Senthilkumar, Gary A Levy, Samuel JK Abraham
bioRxiv 2021.07.08.451700; doi: https://doi.org/10.1101/2021.07.08.451700

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