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      Pharmacological Actions, Molecular Mechanisms, Pharmacokinetic Progressions, and Clinical Applications of Hydroxysafflor Yellow A in Antidiabetic Research

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          Abstract

          Hydroxysafflor yellow A (HSYA), a nutraceutical compound derived from safflower ( Carthamus tinctorius), has been shown as an effective therapeutic agent in cardiovascular diseases, cancer, and diabetes. Our previous study showed that the effect of HSYA on high-glucose-induced podocyte injury is related to its anti-inflammatory activities via macrophage polarization. Based on the information provided on PubMed, Scopus and Wanfang database, we currently aim to provide an updated overview of the role of HSYA in antidiabetic research from the following points: pharmacological actions, molecular mechanisms, pharmacokinetic progressions, and clinical applications. The pharmacokinetic research of HSYA has laid foundations for the clinical applications of HSYA injection in diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. The application of HSYA as an antidiabetic oral medicament has been investigated based on its recent oral delivery system research. In vivo and in vitro pharmacological research indicated that the antidiabetic activities of HSYA were based mainly on its antioxidant and anti-inflammatory mechanisms via JNK/c-jun pathway, NOX4 pathway, and macrophage differentiation. Further anti-inflammatory exploration related to NF- κB signaling, MAPK pathway, and PI3K/Akt/mTOR pathway might deserve attention in the future. The anti-inflammatory activities of HSYA related to diabetes and diabetic complications will be a highlight in our following research.

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          Diabetes as a cardiovascular risk factor: An overview of global trends of macro and micro vascular complications

          Elisa Dal Canto, Antonio Ceriello, Lars Rydén … (2019)
          The global prevalence of diabetes is predicted to increase dramatically in the coming decades as the population grows and ages, in parallel with the rising burden of overweight and obesity, in both developed and developing countries. Cardiovascular disease represents the principal cause of death and morbidity among people with diabetes, especially in those with type 2 diabetes mellitus. Adults with diabetes have 2–4 times increased cardiovascular risk compared with adults without diabetes, and the risk rises with worsening glycaemic control. Diabetes has been associated with 75% increase in mortality rate in adults, and cardiovascular disease accounts for a large part of the excess mortality. Diabetes-related macrovascular and microvascular complications, including coronary heart disease, cerebrovascular disease, heart failure, peripheral vascular disease, chronic renal disease, diabetic retinopathy and cardiovascular autonomic neuropathy are responsible for the impaired quality of life, disability and premature death associated with diabetes. Given the substantial clinical impact of diabetes as a cardiovascular risk factor, there has been a growing focus on diabetes-related complications. While some population-based studies suggest that the epidemiology of such complications is changing and that rates of all-cause and cardiovascular mortality among individuals with diabetes are decreasing in high-income countries, the economic and social burden of diabetes is expected to rise due to changing demographics and lifestyle especially in middle- and low-income countries. In this review we outline data from population-based studies on recent and long-term trends in diabetes-related complications.
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            Prevalence of type 2 diabetes and its complications in India and economic costs to the nation

            R Pradeepa, V N Mohan (2017)
            Diabetes, a major lifestyle disorder, has become a global burden, and the prevalence rates are rising steeply in developing economies. Rapid socioeconomic transition with urbanization and industrialization are the main causes for the global diabetes epidemic. Among developing economies, the highest increase in number of people with diabetes is in China followed by India. In India, the epidemic of diabetes continue to increase and is experiencing a shift in diabetes prevalence from urban to rural areas, the affluent to the less privileged and from older to younger people. Diabetes is a progressive disorder leading to complications, which are broadly divided into small vessel or microvascular disease and large vessel or macrovascular disease. Microvascular complications affect the inner part of the eye-the retina known as diabetic retinopathy, the kidney termed as diabetic nephropathy and the peripheral nerves termed as diabetic neuropathy. The macrovascular complications affect the heart, the brain and the peripheral arteries termed as cardiovascular disease, cerebrovascular disease and peripheral vascular disease, respectively. Given the lifelong expenditure associated with diabetes and its complications, individuals, families and the society are unable to cope with the economic, emotional and social disease burden due to diabetes. The economic burden of diabetes can be reduced by providing universal healthcare coverage, access to affordable medicines and early detection and treatment of the disorder. This emphasizes the need for a multi-prolonged strategy to minimize the burden of diabetes and its complications.
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              Hydroxy-safflor yellow A attenuates Aβ₁₋₄₂-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway.

              Zuo-Hui Zhang, Lin-Jie Yu, Xin-Chen Hui … (2014)
              Beta-amyloid (Aβ)-mediated inflammation plays a critical role in the initiation and progression of Alzheimer׳s disease (AD). Anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of hydroxy-safflor yellow A (HSYA) on Aβ1-42-induced inflammation in AD mice was investigated and the underlying mechanisms were explored. Aβ1-42 was injected into bilateral hippocampi of mice to induce AD models in vivo. Spatial learning and memory of mice were investigated by the Morris water maze test. Activated microglia and astrocytes were examined by immunofluorescence staining for ionized calcium-binding adapter molecule-1 (Iba-1) and glial fibrillary acidic protein (GFAP). The mRNA of inflammatory cytokines were measured using real-time PCR. NF-κB p65 translocation was analyzed by western blotting and immunostaining. IκB and phosphorylation of JAK2 and STAT3 were tested by western blotting. The results showed that HSYA ameliorated the memory deficits in Aβ1-42-induced AD mice. HSYA suppressed Aβ1-42-induced activation of microglia and astrocytes and reduced the mRNA expression of pro-inflammatory mediators. HSYA up-regulated the JAK2/STAT3 pathway and inhibits the activation of NF-κB signaling pathways. Pharmacological inhibition of STAT3 by AG490 reversed the inactivation of p65 and anti-inflammatory effects of HSYA. In conclusion, these results suggest that HSYA protects Aβ1-42-induced AD model through inhibiting inflammatory response, which may involve the JAK2/STAT3/NF-κB pathway. Copyright © 2014 Elsevier B.V. All rights reserved.
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                Author and article information

                Contributors
                Hui Liao:
                ORCID: https://orcid.org/0000-0001-6325-062X
                Journal
                Journal ID (nlm-ta): J Immunol Res
                Journal ID (iso-abbrev): J Immunol Res
                Journal ID (publisher-id): jir
                Title: Journal of Immunology Research
                Publisher: Hindawi
                ISSN (Print): 2314-8861
                ISSN (Electronic): 2314-7156
                Publication date Collection: 2021
                Publication date (Electronic): 13 December 2021
                Volume: 2021
                Electronic Location Identifier: 4560012
                Affiliations
                1School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China
                2Department of Pharmacy, Fifth Hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Taiyuan 030012, China
                Author notes

                Academic Editor: Kai Wang

                Author information
                https://orcid.org/0000-0002-5692-5729
                https://orcid.org/0000-0003-2667-1809
                https://orcid.org/0000-0002-3537-3590
                https://orcid.org/0000-0001-8095-811X
                https://orcid.org/0000-0001-6325-062X
                Article
                DOI: 10.1155/2021/4560012
                PMC ID: 8687819
                PubMed ID: 34938814
                SO-VID: 243647e6-d164-4e8c-9aab-eabcb727e32f
                Copyright © Copyright © 2021 Xilan Zhang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 29 July 2021
                Date revision received : 1 November 2021
                Date accepted : 16 November 2021
                Funding
                Funded by: Key R & D Project of Shanxi Province
                Award ID: 201903D421061
                Funded by: Wu Jieping Medical Foundation
                Award ID: 320.6750.2021-08-10
                Categories
                Subject: Review Article

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