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Phytotherapeutic Agents in Epilepsy
Published in Vikas Kumar, Addepalli Veeranjaneyulu, Herbs for Diabetes and Neurological Disease Management, 2018
Hispidulin is a naturally occurring flavone isolated from Inula viscosa (Fam. Asteraceae) which has been reported to possess antiepileptic properties.37 As excessive release of glutamate is considered to be one of the mechanisms involved in the neuropathology of epilepsy, the effect of hispidulin on endogenous glutamate release in rat synaptosomes has been investigated in this study. Mechanistic studies have shown that hispidulin inhibits the release of glutamate evoked by the potassium channel blocker 4-aminopyridine.
Inhibiting Insulin Resistance and Accumulation of Triglycerides and Cholesterol in the Liver
Published in Christophe Wiart, Medicinal Plants in Asia for Metabolic Syndrome, 2017
Oshima et al. provided evidence that eupafolin, hispidulin, and hispidulin-7 glucoside from Salvia plebeia R. Br. could prevent carbon tetrachloride insults in cultured rat hepatocytes substantiating the hepatoprotective use of the plant.490 The plant elaborates ursolic acid and luteolin-7-O-glucoside,491 which given orally at a daily dose of 2 mg/day for 7 days to Wistar rats lowered glycaemia from 176.1 to 158.1 mg/dL and from 176.1 to 157.6 mg/dL, respectively, and increased glycogen contents in the liver.492 Ursolic acid increased the hepatic expression of phosphoglycogen synthetase kinase-3.492 In the postprandial state, insulin promotes the storage of glucose in the form of glycogen in the liver by activating glycogen synthetase, protein phosphatase 1, inhibition of glycogen phosphorylase (rate-limiting enzyme of glycogenolysis), and inhibiting glycogen synthetase kinase 3 hence activation of glycogen synthetase.493 Both ursolic acid and luteolin-7-O-glucoside decreased plasma cholesterol, low-density lipoprotein, and increased high-density lipoprotein.492 Ursolic acid in CHO/IR cells increased insulin receptor sensitivity with in insulin, increased receptor autophosphorylation and a subsequent activation of downstream phosphatidylinositol 3-kinase resulting in phosphorylation and inactivation of glycogen synthase kinase-3, leading to glycogen synthase activation and glycogen synthesis.491 Glycogen synthase kinase-3 is a key enzyme that suppresses the production of liver glycogen and its activation increases plasma glucose concentration.494 Ursolic acid at a dose of 25 µg/mL repressed the expression of phosphoenolpyruvate carboxykinase in H4IIE cells induced by dexamethasone and 8-bromo-cyclic adenosine monophosphate495 supporting further, at least, the notion of hepatic insulin sensitizing effect of pentacyclic triterpenes.496,497
A role for flavonoids in the prevention and/or treatment of cognitive dysfunction, learning, and memory deficits: a review of preclinical and clinical studies
Published in Nutritional Neuroscience, 2023
Matin Ramezani, Arman Zeinaddini Meymand, Fariba Khodagholi, Hamed Mohammadi Kamsorkh, Ehsan Asadi, Mitra Noori, Kimia Rahimian, Ali Saberi Shahrbabaki, Aisa Talebi, Hanieh Parsaiyan, Sepideh Shiravand, Niloufar Darbandi
GABA is the primary inhibitory neurotransmitter in the mammalian brain, released by up to 40% of neurons. Modulation of GABAAR has been known as one of the major targets to treat neurological and psychological diseases. Flavonoids such as hispidulin [30], luteolin [31], and apigenin [32] have the potent ability against the learning and memory deficits through the modulation of GABAergic neurotransmission. Flavonoids can act on GABAA receptors potentiating GABA actions at low concentrations and inhibiting them at high concentrations in a similar benzodiazepine way of action. Moreover, some flavonoids have agonist activity on the GABA receptors and bind to the receptor when GABA is absent. Flavonoids interact with specific active sites on GABAA receptors [30,32]. Luteolin and apigenin have modulatory actions on GABAA receptors involved in memory improvement. Hispidulin is considered to be a ligand at benzodiazepine binding sites [30]. Luteolin facilitates the kinetics activation of α1β2, α1β2 γ 2, α5β2, and α5β2γ2 receptors, which facilitate the time course of neurotransmitter-evoked responses into the synapses [31].
Synergistic immunosuppressive effect of hispidulin and nepetin mixtures on human T lymphocytes
Published in Immunopharmacology and Immunotoxicology, 2022
Premrutai Thitilertdecha, Varangkana Tantithavorn, Poonsin Poungpairoj, Nattawat Onlamoon
Hispidulin (4′,5,7-trihydroxy-6-methoxyflavone) and nepetin (3′,4′,5,7-tetrahydroxy-6-methoxyflavone) are flavonoids abundantly found in a Thai medicinal plant named Clerodendrum petasites S. Moore (English name: One Root Plant; Thai name: Thao-Yai-Mom) [9] which has been widely prescribed in Thai traditional medicine for treatment of inflammation [10] and is a potential medicinal plant as a complimentary medicine and a good source for new drug development from phytochemicals found within [11]. The plant is often formulated into poultices for skin diseases, such as rash, abscess, urticaria, snakebites, and insect bites [12,13]. Hispidulin was quantified as a predominant compound, being present at 39 µmol (11.7 mg)/g in a dried ethanolic extract, followed by nepetin with 15 µmol (4.7 mg)/g in a dried ethanolic extract from five batches of extraction [9], assuming the composition around 3:1. Because of their appropriate physicochemical properties, hispidulin and nepetin are also qualified as good candidates for skin penetration [9,14]. These provide advantages in using the compounds not only as oral but also topical dosage forms for skin diseases, such as allergic contact dermatitis.
Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid
Published in Immunopharmacology and Immunotoxicology, 2019
Premrutai Thitilertdecha, Varangkana Tantithavorn, Poonsin Poungpairoj, Nattawat Onlamoon
Although anti-inflammatory and immunosuppressive properties of hispidulin and nepetin have been explained by those studies, the information is still not completed as those findings were resulted from experiments in animal models and using isolated compounds from natural plants instead of standard compounds. In this case, the biological properties of the compounds themselves and how they really function in human remain uncertain. On the other hand, the experiments of vanillic acid were performed by using a standard compound providing more reproducible effects for the compound’s pharmacological action; however, its immunomodulatory property still remains ambiguous and controversial from those reports.