Asiatic acid is one of the main active ingredients of the traditional Chinese medicine Centella asiatica. Centella asiatica has been recorded in the "Shen Nong's Materia Medica", and its application in the field of medicine has a history of thousands of years, and its curative effect is definite. As an active ingredient of Centella asiatica, asiatic acid shows a wide range of pharmacological effects, such as anti-inflammatory, skin care, liver protection, anti-depression, hypoglycemia, neuroprotection, and anti-tumor, etc. The development and application of asiatic acid and its derivatives provided a theoretical basis. However, asiatic acid also has shortcomings such as low solubility, low bioavailability, and difficulty in penetrating the blood-brain barrier. Therefore, more extensive structural modification and activity screening studies of asiatic acid are required to meet the needs of drug development.
How to make better use of asiatic acid?
1. Chemical Modification
By evaluating the inhibitory effect of 24 synthetic asiatic acid derivatives on glycogen phosphorylase, it was found that benzyl asiatic acid derivatives showed a stronger inhibitory effect than asiatic acid; a hydrophilic group was introduced at C-28 After treatment, its inhibitory effect on glycogen phosphorylase was significantly reduced or completely lost; at the same time, the study also showed that asiatic acid (2α-OH) had stronger functional activity than kiwifruit acid (2β-OH). The functional groups at positions C-2, 3, 23 and 28 of asiatic acid were modified, and the hepatoprotective effects of the obtained 5 compounds were evaluated. The results showed that the modification of the hydroxyl group at position C-23 was After forming an aldehyde group, it can significantly reduce the degree of injury of primary hepatocytes induced by D-GalN and CCl4; the hepatoprotective effect is significantly enhanced after the introduction of benzyloxy or carbonyl group at the C-2 position; After the deoxygenation of D-GalN, it has obvious alleviation effect on CCl4-induced liver injury, and moderate protective effect on D-GalN-induced liver injury, which are 58.3% and 30.7%, respectively; the introduction of methoxyl group at C-2 position After that, its hepatoprotective effect is basically lost.
The wound-healing activity of 10 chemically synthesized asiatic acid derivatives was evaluated, indicating that methyl ethyl-2-carbonyl-3,23-isopropylidene asiatic acid has a strong ability to promote wound healing and prevent scarring. effect. The structure of asiatic acid was modified by a chemical method to obtain asiatic acid derivative 3β, 23-dihydroxyarsbut-12-en-28-ol. The antibacterial activity of asiatic acid was determined. The bacteriostatic activity was basically lost. The cognitive improvement of 28 kinds of asiatic acid derivatives was evaluated. When C-2 carbonylation, the neuroprotective effect was reduced, and the loss of the C-2 hydroxyl group had little effect on its neuroprotective effect. After methylation and glycosylation of asiatic acid at C-28 position, its cytotoxicity decreased; when C-2 position was cyanated, the cytotoxicity increased sharply, and after the introduction of the benzyloxy group, the cytotoxicity decreased; C-11 carbonyl group After calcification, the cytotoxicity decreased sharply.
2. Biotransformation
At present, there are few studies on the biotransformation of asiatic acid. The structure of asiatic acid was modified by Alternaria longipes, and the C-22 and C-30 hydroxylated asiatic acid derivatives were obtained, which are 2α, 3β, 23, 30-Tetrahydroxy-Usu-12-ene-28-acid, 2α, 3β, 22β, 23-Tetrahydroxy-Usu-12-ene-28-acid and 2α, 3β, 22β, 23, 30- Pentahydroxyursin-12-ene-28-acid. Asiatic acid can be converted with Penicillium lilacinum and Fusarium equiseti to obtain a single conversion product, 2α, 3β, 15α, 23-tetrahydroxyursin-12-ene-28-acid; Streptomyces griseus can convert asiatic acid to obtain 3 metabolites 2α, 3β, 21β, 23-tetrahydroxyursin-12-en-28-acid, 2α, 3β, 23-trihydroxyursul-12-ene-28, 30-diacid and 2α, 3β, 23,30-Tetrahydroxyursin-12-ene-28-acid. Biotransformation of asiatic acid using microorganisms
The main chemical reaction types are hydroxylation and carboxylation, and the substitution sites are mainly C-7, 15, 21, 22, and 30. The relative configuration of the hydroxyl group of the hydroxylation product is β at C-7, 21, and 22. type, the α configuration at C-15.
Why use asiatic acid?
Asiatic acid is one of the most important active components of Centella asiatica, and studies have shown that it has a wide range of pharmacological effects, such as anti-inflammatory, skin care, liver protection, antidepressant, and hypoglycemic, neuroprotective, antitumor, etc.
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