Moronic acid

Antiviral Res. 2010 Mar;85(3):490-5.

Inhibition of the Epstein-Barr virus lytic cycle by moronic acid.[Pubmed: 19969023]

Epstein-Barr virus (EBV) expresses two transcription factors, Rta and Zta, during the immediate-early stage of the lytic cycle to activate the transcription of viral lytic genes.
METHODS AND RESULTS:
Our immunoblotting and flow cytometry analyses find that Moronic acid, found in galls of Rhus chinensis and Brazilian propolis, at 10microM inhibits the expression of Rta, Zta, and an EBV early protein, EA-D, after lytic induction with sodium butyrate. This study also finds that Moronic acids inhibits the capacity of Rta to activate a promoter that contains an Rta-response element, indicating that Moronic acid interferes with the function of Rta. On the other hand, Moronic acid does not appear to influence with the transactivation function of Zta. Therefore, the lack of expression of Zta and EA-D after Moronic acid treatment is attributable to the inhibition of the transactivation functions of Rta. Because the expression of Zta, EA-D and many EBV lytic genes depends on Rta, the treatment of P3HR1 cells with Moronic acid substantially reduces the numbers of EBV particles produced by the cells after lytic induction.
CONCLUSIONS:
This study suggests that Moronic acid is a new structural lead for anti-EBV drug development.

J Med Chem. 2010 Apr 22;53(8):3133-41.

Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.[Pubmed: 20329730]

METHODS AND RESULTS:
In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3' dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, Moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class.
CONCLUSIONS:
This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC(50): 0.0006 microM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.

J Nat Prod. 2001 Oct;64(10):1278-81.

Anti-AIDS agents. 48.(1) Anti-HIV activity of moronic acid derivatives and the new melliferone-related triterpenoid isolated from Brazilian propolis.[Pubmed: 11678650]

METHODS AND RESULTS:
A new triterpenoid named melliferone (1), three known triterpenoids, Moronic acid (2), anwuweizonic acid (3), and betulonic acid (4), and four known aromatic compounds (5-8) were isolated from Brazilian propolis and tested for anti-HIV activity in H9 lymphocytes.
CONCLUSIONS:
Moronic acid (2) showed significant anti-HIV activity (EC(50) <0.1 microg/mL, TI >186) and was modified to develop more potent anti-AIDS agents.

J Pharmacol Exp Ther. 1999 Apr;289(1):72-8.

Anti-herpes simplex virus activity of moronic acid purified from Rhus javanica in vitro and in vivo.[Pubmed: 10086989]

Rhus javanica, a medicinal herb, has been shown to exhibit oral therapeutic anti-herpes simplex virus (HSV) activity in mice.
METHODS AND RESULTS:
We purified two major anti-HSV compounds, Moronic acid and betulonic acid, from the herbal extract by extraction with ethyl acetate at pH 10 followed by chromatographic separations and examined their anti-HSV activity in vitro and in vivo. Moronic acid was quantitatively a major anti-HSV compound in the ethyl acetate-soluble fraction. The effective concentrations for 50% plaque reduction of Moronic acid and betulonic acid for wild-type HSV type 1 (HSV-1) were 3.9 and 2.6 microgram/ml, respectively. The therapeutic index of Moronic acid (10.3-16.3) was larger than that of betulonic acid (6.2). Susceptibility of acyclovir-phosphonoacetic acid-resistant HSV-1, thymidine kinase-deficient HSV-1, and wild-type HSV type 2 to Moronic acid was similar to that of the wild-type HSV-1. When this compound was administered orally to mice infected cutaneously with HSV-1 three times daily, it significantly retarded the development of skin lesions and/or prolonged the mean survival times of infected mice without toxicity compared with the control. Moronic acid suppressed virus yields in the brain more efficiently than those in the skin. This was consistent with the prolongation of mean survival times.
CONCLUSIONS:
Thus, Moronic acid was purified as a major anti-HSV compound from the herbal extract of Rhus javanica. Mode of the anti-HSV activity was different from that of ACV. Moronic acid showed oral therapeutic efficacy in HSV-infected mice and possessed novel anti-HSV activity that was consistent with that of the extract.

Phytomedicine. 2013 May 15;20(7):571-6.

Antihyperglycemic and sub-chronic antidiabetic actions of morolic and moronic acids, in vitro and in silico inhibition of 11β-HSD 1.[Pubmed: 23453304 ]

Morolic acid(1) and moronic (2) acid are the main constituents of acetonic extract from Phoradendron reichenbachianum (Loranthaceae), a medicinal plant used in Mexico for the treatment of diabetes. The aim of the current study was to establish the sub-acute antidiabetic and antihyperlipidemic effects of compounds 1 and 2 over non insulin-dependent diabetic rat model. Also, to determine the antihyperglycemic action on normoglycemic rats by oral glucose tolerance test.
METHODS AND RESULTS:
Daily-administered morolic acid(1) and Moronic acid(2)(50 mg/kg) significantly lowered the blood glucose levels at 60% since first day until tenth day after treatment than untreated group (p<0.05). Moreover, analyzed blood samples obtained from diabetic rats indicated that both compounds diminished plasmatic concentration of cholesterol (CHO) and triglycerides (TG), returning them to normal levels (p<0.05). Also, pretreatment with 50 mg/kg of each compound induced significant antihyperglycemic effect after glucose and sucrose loading (2 g/kg) compared with control group (p<0.05). In vitro studies showed that compounds 1 and 2 induced inhibition of 11β-HSD 1 activity at 10 μM. However, in silico analysis of the pentaclyclic triterpenic acids on 11β-HSD 1 revealed that all compounds had high docking scores and important interactions with the catalytic site allowing them to inhibit 11β-HSD 1 enzyme.
CONCLUSIONS:
In conclusion, morolic acid and Moronic acid have shown sustained antidiabetic and antihyperglycemic action possibly mediated by an insulin sensitization with consequent changes of glucose, cholesterol and triglycerides, in part mediated by inhibition of 11β-HSD 1 as indicated by in vitro and in silico studies.