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      Diverse Pharmacological Activities and Potential Medicinal Benefits of Geniposide

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          Abstract

          Geniposide is a well-known iridoid glycoside compound and is an essential component of a wide variety of traditional phytomedicines, for example, Gardenia jasminoides Elli (Zhizi in Chinese), Eucommia ulmoides Oliv. (Duzhong in Chinese), Rehmannia glutinosa Libosch. (Dihuang in Chinese), and Achyranthes bidentata Bl. (Niuxi in Chinese). It is also the main bioactive component of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides Ellis. Increasing pharmacological evidence supports multiple medicinal properties of geniposide including neuroprotective, antidiabetic, hepatoprotective, anti-inflammatory, analgesic, antidepressant-like, cardioprotective, antioxidant, immune-regulatory, antithrombotic, and antitumoral effects. It has been proposed that geniposide may be a drug or lead compound for the prophylaxis and treatment of several diseases, such as Alzheimer's disease, Parkinson's disease, diabetes and diabetic complications, ischemia and reperfusion injury, and hepatic disorders. The aim of the present review is to give a comprehensive summary and analysis of the pharmacological properties of geniposide, supporting its use as a medicinal agent.

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          Protection against cardiac hypertrophy by geniposide involves the GLP-1 receptor / AMPKα signalling pathway.

          Zhen-Guo Ma, Jia Bing Dai, Wen-Bin Zhang … (2016)
          Activation of glucagon-like peptide-1 (GLP-1) receptor exerts a range of cardioprotective effects. Geniposide is an agonist of GLP-1 receptor, but its role in cardiac hypertrophy remains completely unknown. Here, we have investigated its protective effects and clarified the underlying molecular mechanisms.
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            Antidepressant-like effect of geniposide on chronic unpredictable mild stress-induced depressive rats by regulating the hypothalamus-pituitary-adrenal axis.

            Li Cai, Rong Li, Wen-jian Tang … (2015)
            Geniposide as the major active component of Gardenia jasminoides Ellis has neuroprotective activity. This study elucidated the potential antidepressant-like effect of geniposide and its related mechanisms using a depression rat model induced by 3 consecutive weeks of chronic unpredictable mild stress (CUMS). Sucrose preference test, open field test (OFT) and forced swimming test (FST) were applied to evaluate the antidepressant effect of geniposide. Adrenocorticotropic hormone (ACTH) and corticosterone (CORT) serum levels, adrenal gland index and hypothalamic corticotrophin-releasing hormone (CRH) mRNA expression were measured to assess the activity of hypothalamus-pituitary-adrenal (HPA) axis. Hypothalamic glucocorticoid receptor α (GRα) mRNA expression and GRα protein expression in hypothalamic paraventricular nucleus (PVN) were also determined by real-time PCR and immunohistochemistry, respectively. We found that geniposide (25, 50, 100mg/kg) treatment reversed the CUMS-induced behavioral abnormalities, as suggested by increased sucrose intake, improved crossing and rearing behavior in OFT, shortened immobility and prolonged swimming time in FST. Additionally, geniposide treatment normalized the CUMS-induced hyperactivity of HPA axis, as evidenced by reduced CORT serum level, adrenal gland index and hypothalamic CRH mRNA expression, with no significant effect on ACTH serum level. Moreover, geniposide treatment upregulated the hypothalamic GRα mRNA level and GRα protein expression in PVN, suggesting geniposide could recover the impaired GRα negative feedback on CRH expression and HPA axis. These aforementioned therapeutic effects of geniposide were essentially similar to fluoxetine. Our results indicated that geniposide possessed potent antidepressant-like properties that may be mediated by its effects on the HPA axis.
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              Geniposide ameliorates learning memory deficits, reduces tau phosphorylation and decreases apoptosis via GSK3β pathway in streptozotocin-induced alzheimer rat model.

              Albert Liu, Lin Li, Y. Jiang … (2014)
              Intracerebral-ventricular (ICV) injection of streptozotocin (STZ) induces an insulin-resistant brain state that may underlie the neural pathogenesis of sporadic Alzheimer disease (AD). Our previous work showed that prior ICV treatment of glucagon-like peptide-1 (GLP-1) could prevent STZ-induced learning memory impairment and tau hyperphosphorylation in the rat brain. The Chinese herbal medicine geniposide is known to relieve symptoms of type 2 diabetes. Because geniposide is thought to act as a GLP-1 receptor agonist, we investigated the potential therapeutic effect of geniposide on STZ-induced AD model in rats. Our result showed that a single injection of geniposide (50 μM, 10 μL) to the lateral ventricle prevented STZ-induced spatial learning deficit by about 40% and reduced tau phosphorylation by about 30% with Morris water maze test and quantitative immunohistochemical analysis, respectively. It has been known that tau protein can be phosphorylated by glycogen synthase kinase-3 (GSK3) and STZ can increase the activity of GSK3β. Our result with Western blot analysis showed that central administration of geniposide resulted in an elevated expression of GSK3β(pS-9) but suppressed GSK3β(pY-216) indicating that geniposide reduced STZ-induced GSK3β hyperactivity. In addition, ultrastructure analysis showed that geniposide averted STZ-induced neural pathology, including paired helical filament (PHF)-like structures, accumulation of vesicles in synaptic terminal, abnormalities of endoplasmic reticulum (ER) and early stage of apoptosis. In summary, our study suggests that the water soluble and orally active monomer of Chinese herbal medicine geniposide may serve as a novel therapeutic agent for the treatment of sporadic AD. © 2013 International Society of Neuropathology.
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                Author and article information

                Contributors
                Hong Zhang:
                ORCID: http://orcid.org/0000-0002-6191-0046
                Cheng Peng:
                ORCID: http://orcid.org/0000-0001-7561-6131
                Journal
                Journal ID (nlm-ta): Evid Based Complement Alternat Med
                Journal ID (iso-abbrev): Evid Based Complement Alternat Med
                Journal ID (publisher-id): ECAM
                Title: Evidence-based Complementary and Alternative Medicine : eCAM
                Publisher: Hindawi
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date Collection: 2019
                Publication date (Electronic): 16 April 2019
                Publication date PMC-release: 16 April 2019
                Volume: 2019
                Electronic Location Identifier: 4925682
                Affiliations
                1Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
                2Library, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
                3School of Pharmacy and Biomolecular Sciences, Faculty of Science, Liverpool John Moores University, Liverpool L3 3AF, UK
                4Institute of Interdisciplinary Medical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
                Author notes

                Academic Editor: Jairo Kennup Bastos

                Author information
                http://orcid.org/0000-0002-4895-3594
                http://orcid.org/0000-0002-6191-0046
                http://orcid.org/0000-0001-7561-6131
                Article
                DOI: 10.1155/2019/4925682
                PMC ID: 6500620
                PubMed ID: 31118959
                SO-VID: 31130a51-f30a-4303-bdb0-37b2103702da
                Copyright © Copyright © 2019 Yan-Xi Zhou 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 : 2 January 2019
                Date accepted : 19 March 2019
                Funding
                Funded by: Chengdu University of Traditional Chinese Medicine
                Award ID: ZRQN1655
                Award ID: YXRC2018006
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Complementary & Alternative medicine
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine

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