Chronic diseases, including metabolic syndrome related to sugar and lipid metabolic disorders, are the leading causes of premature death around the world. Novel treatment strategies without undesirable effects are urgently needed. As a natural functional ingredient, puerarin is a promising alternative for the treatment of sugar and lipid metabolic disorders. However, the applications of puerarin are limited due to its poor solubility and short half-life. Various drug delivery systems have been investigated to improve the bioavailability of puerarin. This review summarizes the mechanisms involved in the beneficial action of puerarin: suppressing the release of glucose and FFA; regulating the transport of glucose and fatty acids; acting on the PI3K-Akt and AMPK signaling pathways to decrease the synthesis of glucose and fatty acids; acting on the PPAR signaling pathway to promote β-oxidation; and improving insulin secretion and sensitivity. In addition, the preparation technologies used to improve the bioavailability of puerarin are also summarized in this review, in the hope of helping to promote the application of puerarin.

BACKGROUND: Pueraria is the common name of the dried root of either Pueraria montana var. lobata (Willd.) Maesen & S.M.Almeida ex Sanjappa & Predeep (syn. Pueraria lobata (Willd.) Ohwi) or Pueraria montana var. thomsonii (Benth.) M.R.Almeida (syn. Pueraria thomsonii Benth.). Puerarin is a C-glucoside of the isoflavone daidzein extracted from Pueraria. It has been widely investigated to explore its therapeutic role in eye diseases and the molecular mechanisms.
OBJECTIVE: To collect the available literature from 2000 to 2022 on puerarin in the treatment of ocular diseases and suggest the future required directions to improve its medicinal value.
METHODS: The content of this review was obtained from databases such as Web of Science, PubMed, Google Scholar, China National Knowledge Infrastructure (CNKI), and the Wanfang Database.
RESULTS: The search yielded 428 articles, of which 159 articles were included after excluding duplicate articles and articles related to puerarin but less relevant to the topic of the review. In eleven articles, the bioavailability of puerarin was discussed. Despite puerarin possesses diverse biological activities, its bioavailability on its own is poor. There are 95 articles in which the therapeutic mechanisms of puerarin in ocular diseases was reported. Of these, 54 articles discussed the various signalling pathways related to occular diseases affected by puerarin. The other 41 articles discussed specific biological activities of puerarin. It plays a therapeutic role in ophthalmopathy via regulating nuclear factor kappa-B (NF-ĸB), mitogen-activated protein kinases (MAPKs), PI3K/AKT, JAK/STAT, protein kinase C (PKC) and other related pathways, affecting the expression of tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1), superoxide dismutase (SOD), B-cell lymphoma-2 (Bcl-2) and other cytokines resulting in anti-inflammatory, antioxidant and anti-apoptotic effects. The clinical applications of puerarin in ophthalmology were discussed in 25 articles. Eleven articles discussed the toxicity of puerarin. The literature suggests that puerarin has a good curative effect and can be used safely in clinical practice.
CONCLUSIONS: This review has illustrated the diverse applications of puerarin acting on ocular diseases and suggested that puerarin can be used for treating diabetic retinopathy, retinal vascular occlusion, glaucoma and other ocular diseases in the clinic. Some ocular diseases are the result of the combined action of multiple factors, and the effect of puerarin on different factors needs to be further studied to improve a more complete mechanism of action of puerarin. In addition, it is necessary to increase the number of subjects in clinical trials and conduct clinical trials for other ocular diseases. The information presented here will guide future research studies.

Osteoporosis is a systemic bone disease characterized by decreased bone mass and quality and bone micro‑architecture degradation. Its primary cause is disorder of bone metabolism: Over‑formation of osteoclasts, resulting in increased bone resorption and insufficient osteogenesis. Traditional herbal flavonoids can be used as alternative drugs to prevent and treat osteoporosis due to their wide range of sources, structural diversity and less adverse effects. The present paper reviewed six flavonoids, including quercetin, icariin, hesperitin, naringin, chrysin and pueraria, that promote bone formation and have been widely studied in the literature over the past five years, with the aim of providing novel ideas for the development of drugs for bone‑associated disease.

Chronic wounds have a high disease burden and significantly influence patient quality of life. The development of chronic wounds is multifactorial and thus adequate management and care is often difficult to achieve. Chronic diseases, malnutrition, smoking, immune dysregulation, and age contribute to chronic wound development. Treatment options include adequately addressing underlying conditions and selecting appropriate topical preparations which enhance and promote healing of different wounds based on an understanding of wound healing pathophysiology. Puerarin, a naturally occurring flavinoid, may offer therapeutic potential for addressing etiologies as well as managing wound beds due to its anti-inflammatory, anti-oxidative, pro-angiogenic, and anesthetic properties.

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Cardiovascular diseases (CVDs) are now the leading cause of mortality and morbidity worldwide，resulting in a large global economic burden. Recently, complementary and alternative medicine, such as traditional Chinese medicine (TCM) have received great attention. Puerarin (Pue) is an isoflavone isolated from the roots of Pueraria lobata (Willd.) Ohwi (also named \"Ge gen\" in China), and is a versatile TCM herb used for the treatment of fever, diarrhea, diabetes mellitus CVDs and cerebrovascular diseases. Numerous lines ofin vitro studies, as well as in vivo animal experiments have established that Pue offers beneficial roles against the progression of atherosclerosis, ischemic heart diseases, heart failure hypertension and arrhythmia by inhibiting pathological processes, such as the mitigation of endothelium injury, protection against inflammation, the disturbance of lipid metabolism, protection against ischemic reperfusion injury, anti-myocardial remodeling and other effects. Here, we provide a systematic overview of the pharmacological actions and molecular targets of Pue in cardiovascular disease prevention and treatment, to provide insights into the therapeutic potential of Pue in treating cardiovascular diseases.

In recent years, with the improvement of people\'s living standard and the change of diet structure, liver disease and its related complications have become a significant public health problem globally. Pueraria lobata (Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep) belongs to the genus Pueraria, which is widely planted and used as medicine and food in Asia with a long history. A variety of natural active products, including puerarin, daidzein, formononetin, genistein, and soyasaponin, have been isolated and identified from pueraria lobata. A large number of studies have shown that various natural active products of pueraria lobata can play a protective role in different types of liver diseases by regulating oxidative stress, inflammatory response, lipid metabolism, etc. In this review, we focused on the protective effects of isoflavones and triterpenoid saponins from pueraria lobata on the liver through different targeted therapeutic mechanisms. What\'s more, we summarized their therapeutic potential for different types of liver diseases to provide evidence for their clinical application.

Pueraria species are listed in the Chinese Pharmacopeia and are being used for the treatment of various health ailments and in protecting health. Puerarin, a chemotaxonomic marker of Pueraria, received investigational drug status for the treatment of alcohol abuse and listed in DRUGBANK database. The purpose of this review is to provide insights on health benefits of Pueraria, its bioactive constituents and molecular mechanisms. The information is retrieved from various databases. The most investigated plant part is tuber and the major bioactive constituents are isoflavones. The Pueraria is reported to possess a lots of health benefits on brain, liver, heart, kidney, bone, stomach, muscle, skin, and reproductive system. Pueraria also shown beneficial effects in postmenopausal women. In this review, the scientific information on Pueraria reported until May 2020 were analysed and summarized logically to appreciate its health benefits and to identify research gaps.

Cancer is one of the prominent global causes of death and the foremost worldwide health concern. Despite unprecedented progress in cancer chemoprevention, a vast number of cancers, however, remain an undefeatable challenge for treatment modalities. Immense therapeutic activities of puerarin contribute to its use in various health disorders. In this review, we explored the potential molecular mechanisms and targets of puerarin, proving its potential as a novel anticancer agent, for future cancer therapy and chemoprevention. Several mechanisms account for anticancer activity of puerarin which includes downregulation of NF-kB signalling pathway, mTOR signalling pathway, PI3K and BCl-2 proteins and upregulation of miR-16, caspase proteins, c- Jun N terminal kinase and extracellular signal-regulated kinase 1/2. These alterations result in inhibition of cancer cell proliferation and/or induction of apoptosis. Understanding the molecular mechanisms involved in chemotherapy and chemoprevention could aid in the more pronounced exploration of puerarin in effective cancer treatment.

OBJECTIVE: Ovariectomy (OVX)-induced murine model is widely used for postmenopausal osteoporosis study. Our current study was conducted to systematically review and essentially quantified the bone mass enhancing effect of puerarin on treating OVX-induced postmenopausal osteoporosis in murine model.
METHODS: Literatures from PUBMED, EMBASE, and CNKI were involved in our searching strategy by limited the inception date to January 9th, 2019. Moreover, the enhancing effect of puerarin on bone mass compared to OVX-induced rats is evaluated by four independent reviewers. Finally, all the data were extracted, quantified and analyzed via RevMan, besides that in our current review study, we assessed the methodological quality for each involved study.
RESULTS: Based on the searching strategy, eight randomization studies were finally included in current meta-analysis and systematic review. According to the data analysis by RevMan, puerarin could improve bone mineral density (BMD); (eight studies, n=203; weighted mean difference, 0.05; 95% CI, 0.03-0.07; P<0.0001) using a random-effects model. There is no significant difference between puerarin and estrogen (seven studies, n=184; weighted mean difference, 0.00; 95% CI, -0.01 to 0.00; P=0.30).
CONCLUSIONS: Puerarin showed upregulating effects on bone mass in OVX-induced postmenopausal osteoporosis in murine model. More studies of the effect of puerarin on bone density in OVX animals are needed.