Puerarin: a hepatoprotective drug from bench to bedside

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Abstract

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.

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AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

Joungmok Kim, Mondira Kundu, Benoit Viollet … (2011)

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

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Burden of liver diseases in the world

Sumeet K Asrani, Harshad Devarbhavi, John Eaton … (2019)

Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.

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The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

Elena Buzzetti, Massimo Pinzani, Emmanuel Tsochatzis (2016)

Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. Despite its high prevalence, only a small minority of affected patients develops inflammation and subsequently fibrosis and chronic liver disease, while most of them only exhibit simple steatosis. In this context, the full understanding of the mechanisms underlying the development of NAFLD and non-alcoholic steatohepatitis (NASH) is of extreme importance; despite advances in this field, knowledge on the pathogenesis of NAFLD is still incomplete. The 'two-hit' hypothesis is now obsolete, as it is inadequate to explain the several molecular and metabolic changes that take place in NAFLD. The "multiple hit" hypothesis considers multiple insults acting together on genetically predisposed subjects to induce NAFLD and provides a more accurate explanation of NAFLD pathogenesis. Such hits include insulin resistance, hormones secreted from the adipose tissue, nutritional factors, gut microbiota and genetic and epigenetic factors. In this article, we review the factors that form this hypothesis.

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Author and article information

Contributors

Xin Zhou: zhouxinmm@swmu.edu.cn

Hui Chen: fairysusan@126.com

Zhi Li: lizhi_swmu@126.com

Journal

Journal ID (nlm-ta): Chin Med

Journal ID (iso-abbrev): Chin Med

Title: Chinese Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1749-8546

Publication date (Electronic): 8 October 2024

Publication date PMC-release: 8 October 2024

Publication date Collection: 2024

Volume: 19

Electronic Location Identifier: 139

Affiliations

[1 ]GRID grid.410578.f, ISNI 0000 0001 1114 4286, The Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Digestive System Diseases of Luzhou City, , Affiliated Traditional Medicine Hospital of Southwest Medical University, ; Luzhou, 646000 China

[2 ]GRID grid.488387.8, Department of Spleen and Stomach Diseases, , The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, ; Luzhou, 646000 Sichuan China

[3 ]Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, ( https://ror.org/00g2rqs52) Luzhou, 646000 Sichuan China

[4 ]Department of Pediatrics, The Affiliated Hospital, Southwest Medical University, ( https://ror.org/00g2rqs52) Luzhou, 646000 Sichuan China

Author information

Yi-Xiang He http://orcid.org/0009-0003-6425-0519

Article

Publisher ID: 1011

DOI: 10.1186/s13020-024-01011-y

PMC ID: 11460048

PubMed ID: 39380120

SO-VID: 19bac81f-0d3c-442c-a58d-7cbed71c9cdb

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 6 July 2024

Date accepted : 22 September 2024

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100012542, Sichuan Province Science and Technology Support Program;

Award ID: 2022YFS0624

Award Recipient : Zhi Li

Funded by: FundRef http://dx.doi.org/10.13039/501100016350, Sichuan Provincial Administration of Traditional Chinese Medicine;

Award ID: 2023ZD008

Award ID: 2023MS335

Award Recipient : Hui Chen Zhi Li

Funded by: FundRef http://dx.doi.org/10.13039/501100009579, Health Department of Sichuan Province;

Award ID: Sichuan Cadre Research 2024-2001

Award Recipient : Zhi Li

Funded by: the Science and Technology Programme of Southwest Medical University

Award ID: 2022-CXTD-01

Award Recipient : Zhi Li

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: puerarin,liver disease,pharmacological effects,chinese herbal medicine

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ScienceOpen disciplines: Complementary & Alternative medicine

Keywords: puerarin, liver disease, pharmacological effects, chinese herbal medicine

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Puerarin: a hepatoprotective drug from bench to bedside

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Most cited references 140

AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

Burden of liver diseases in the world

The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD).

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