Recensione

Bibliografia__________________________________________________________________________

Wang C, Gong X, Bo A, Zhang L, Zhang M, Zang E, Zhang C, Li M. Iridoids: Research Advances in Their Phytochemistry, Biological Activities, and Pharmacokinetics. Molecules. 2020 Jan 10;25(2):287. doi: 10.3390/molecules25020287. 

Abstract. Iridoids are a class of active compounds that widely exist in the plant kingdom. In recent years, with advances in phytochemical research, many compounds with novel structure and outstanding activity have been identified. Iridoid compounds have been confirmed to mainly exist as the prototype and aglycone and Ι and II metabolites, by biological transformation. These metabolites have been shown to have neuroprotective, hepatoprotective, anti-inflammatory, antitumor, hypoglycemic, and hypolipidemic activities. This review summarizes the new structures and activities of iridoids identified locally and globally, and explains their pharmacokinetics from the aspects of absorption, distribution, metabolism, and excretion according to the differences in their structures, thus providing a theoretical basis for further rational development and utilization of iridoids and their metabolites.

Kou Y, Li Z, Yang T, Shen X, Wang X, Li H, Zhou K, Li L, Xia Z, Zheng X, Zhao Y. Therapeutic potential of plant iridoids in depression: a review. Pharm Biol. 2022 Dec;60(1):2167-2181. doi: 10.1080/13880209.2022.2136206. 

Abstract. Context: Depression is a mental disorder characterized by low mood, reduced interest, impaired cognitive function, and vegetative symptoms such as sleep disturbances or poor appetite. Iridoids are the active constituents in several Chinese classical antidepressant formulae such as Yueju Pill, Zhi-Zi-Hou-Po Decoction, Zhi-Zi-Chi Decoction, and Baihe Dihuang Decoction. Parallel to their wide usages, iridoids are considered potential lead compounds for the treatment of neurological diseases. Objective: The review summarizes the therapeutic potential and molecular mechanisms of iridoids in the prevention or treatment of depression and contributes to identifying research gaps in iridoids as potential antidepressant medication.....Discussion and conclusions: Iridoids exert antidepressant effects by elevating monoamine neurotransmitters, reducing pro-inflammatory factors, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, increasing brain-derived neurotrophic factor (BDNF) and its receptors, and elevating intestinal microbial abundance. Further detailed studies on the pharmacokinetics, bioavailability, and key molecular targets of iridoids are also required in future research, ultimately to provide improvements to current antidepressant medications.

Usmanov D, Azamatov A, Baykuziyev T, Yusupova U, Rasulev B. Chemical constituents, anti-inflammatory and analgesic activities of iridoids preparation from Phlomoides labiosa bunge. Nat Prod Res. 2023 May;37(10):1709-1713. doi: 10.1080/14786419.2022.2104274. 

Abstract. This study reports the isolation of iridoids and cycloartane glycosides from the aerial parts of Phlomoides labiosa Bunge. Six compounds were isolated and the chemical structures were identified as phlorigidoside С (1), 8-O-acetylharpagide (2), shanzhiside methyl ester (3), cyclosiversioside A (4), cyclosiversioside E (5), and cyclosiversioside C (6). Compounds 4-6 are reported for the first time in this plant. In addition, anti-inflammatory and analgesic activities of iridoid fraction were studied. The sum of iridoids (SI) with intragastric administration is 5.2 and 52.5 times less toxic, than such market drugs as analgin and diclofenac sodium, respectively. In terms of the latitude of analgesic action (LD50/ED50), the SI exceeds analgin by 19.2 times and diclofenac sodium by 16 times. The anti-inflammatory and analgesic activities of the sum of iridoids were confirmed to be effective and nontoxic, and exceed known drugs diclofenac sodium and analgin (metamizole sodium).

Ling SK, Tanaka T, Kouno I. Effects of iridoids on lipoxygenase and hyaluronidase activities and their activation by beta-glucosidase in the presence of amino acids. Biol Pharm Bull. 2003 Mar;26(3):352-6. doi: 10.1248/bpb.26.352. 

Abstract. Enzyme inhibitory activities of 14 iridoids previously obtained from two Malaysian medicinal plants, Saprosma scortechinii and Rothmannia macrophylla, were evaluated in vitro using soybean lipoxygenase and bovine testis hyaluronidase. Most of the iridoids, including asperulosidic acid, paederosidic acid, and an epimeric mixture of gardenogenins A and B, did not show any effect on the enzyme activities, except for the bis-iridoids, which inhibited the lipoxygenase activity with their IC(50) values of approximately 1.3 times that of a known inhibitor, fisetin. Structural modification of asperulosidic acid and paederosidic acid through enzymatic hydrolysis by beta-glucosidase resulted in their inhibition towards the enzyme activities, and these activities were enhanced by the presence of some amino acids (lysine, leucine or glutamic acid) or ammonium acetate. Mixtures of gardenogenins A and B; isomers of non-glucosidic iridoids, incubated with amino acid or ammonium acetate did not show any inhibitory effect on the enzyme activities during the 6 h incubation period, except for lysine where spontaneous reaction between the iridoids and amino acid resulted in the inhibition of lipoxygenase activity. The results from these biomimetic reactions suggested that the iridoid aglycons and the intermediates formed by these reactive species could inhibit the enzyme activities, and thus substantiate previous reports that the formation of iridoidal aglycons is a prerequisite for the iridoid glycosides to demonstrate some of the biological activities. In addition, the results also indicated that it is worthwhile to further explore these intermediates as potential anti-inflammatory agents.

Dal Piaz F, Vassallo A, Temraz A, Cotugno R, Belisario MA, Bifulco G, Chini MG, Pisano C, De Tommasi N, Braca A. A chemical-biological study reveals C9-type iridoids as novel heat shock protein 90 (Hsp90) inhibitors. J Med Chem. 2013 Feb 28;56(4):1583-95. doi: 10.1021/jm301398y. 

Abstract. The potential of heat shock protein 90 (Hsp90) as a therapeutic target for numerous diseases has made the identification and optimization of novel Hsp90 inhibitors an emerging therapeutic strategy. A surface plasmon resonance (SPR) approach was adopted to screen some iridoids for their Hsp90 α binding capability. Twenty-four iridoid derivatives, including 13 new natural compounds, were isolated from the leaves of Tabebuia argentea and petioles of Catalpa bignonioides. Their structures were elucidated by NMR, electrospray ionization mass spectrometry, and chemical methods. By means of a panel of chemical and biological approaches, four iridoids were demonstrated to bind Hsp90 α. In particular, the dimeric iridoid argenteoside A was shown to efficiently inhibit the chaperone in biochemical and cellular assays. Our results disclose C9-type iridoids as a novel class of Hsp90 inhibitors.