Absolute Stereostructures of Polypodane-Type Triterpenes, Myrrhanol A and Myrrhanone A, from Guggul-Gum Resin (the Resin of Balsamodendron mukul)

Abstract

Guggul-gum resin [the resin of Balsamodendron (ϭCom-miphora) mukul HOOK. (Burseraceae)] is produced by drying the milky-white sap of the tree (15-20 years old) for one year. This natural medicine is prescribed in the form of direct mixtures with powders or extracts of other natural medicines for use as anti-obesity, antiinflammatory, antibacterial, anticoagulant, and anti-atherosclerosis agents in Ayurvedic folk medicine in India. Previously, the antiinflammatory activity of guggul has been reported, [1][2][3] and guggulsterone, a constituent of guggul, activates lipolytic enzymes, inhibits hepatic cholesterol biosynthesis, and reduces the total serum lipid and total serum cholesterol levels. 4,5) A similar natural medicine, myrrh [the resin of Balsamodendron (or Commiphora) myrrha NEES] was used by the Egyptians for embalming, and by the Jews as an anointing oil. The sesquiterpene constituents isolated from myrrh, furanoeudesma-1,3-diene and curzarene, have analgesic effects that are blocked by naloxone, explaining the use of myrrh as a painkiller in ancient times. 6) However, because of its toxicity, myrrh is not used in medicines today, except as a mouthwash in India.In the course of our characterization studies on traditional Ayurvedic medicines, [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] we found that the 50% aqueous methanolic extract of guggul (the resin of B. mukul) showed an anti-inflammatory effect on adjuvant-induced air pouch granuloma in mice. From the extract, two new polypodanetype triterpenes, myrrhanol A (1) and myrrhanone A (2), were isolated as the active components. 7) Furthermore, the methanolic extract of this natural medicine was found to exhibit an inhibitory effect on nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages. From the methanolic extract, we isolated three polypodanetype triterpenes named myrrhanol B (3), myrrhanones B (4), and A acetate, and an octanordammarane-type triterpene termed epimansumbinol, together with 17 known constituents.8) This paper presents a full account of the isolation and characterization of myrrhanol A (1) and myrrhanone A (2).The 50% aqueous methanolic extract (5.68% from natural medicine) of the resin of guggul-gum was partitioned in an ethyl acetate (EtOAc) and water mixture to furnish the EtOAc-and H 2 O-soluble fractions. The EtOAc-soluble fraction was subjected to normal and reversed phase silica gel column chromatographies, and finally HPLC, to give two new polypodane-type triterpenes, myrrhanol A 7) (1, 0.036%) and myrrhanone A 7) (2, 0.026%), together with four polypodane-type triterpenes, myrrhanol (Table 1) spectra of 1, which were assigned by various NMR experiments, 27) showed a presence of seven tertiary methyls [d 0.75, 0.79, 0.98, 1.13, 1.65 (s, 24, 25, 23, 26, 29-H 3 ), 1.60 (s, 27, 28-H 3 )], a methine bearing an oxygen function [d 3.21 (dd, Jϭ4.9, 11.6 Hz,], a methylene bearing an oxygen function [d 3.96 (s, 30-H 2 )], and three trisubstituted olefins [d 5.12 (dd, Jϭ...

Identification of a novel agonist of peroxisome proliferator-activated receptors α and γ that may contribute to the anti-diabetic activity of guggulipid in Lepob/Lepob mice

“…It constituted 9.5% of guggulipid (Table 1). Two bicyclic triterpenoids previously identified by others [16,17] were also found in Fraction 5. These were octahydro-6-hydroxy-5-(13-hydroxy-4,8,12-trimethyl-3,7,11-tridecatrienyl)-1,1,4a,6-tetramethyl-[4aS-[4aα,5α(3E,7E,11E),6-β,8aβ]]-2(1H)-naphthalenone (also termed myrrhanone A or commipherol) and decahydro-5-[(3E,7E,11E)-13-hydroxy-4,8,12-trimethyl-3,7,11-tridecatrienyl]-1,1,4a,6-tetramethyl-(2S,4aS,5R,6R,8aS)-2,6-naphthalenediol (termed myrrhanol A) (Fig.…”

“…However, PPARγ agonists stimulate the differentiation of preadipocytes to adipocytes [24,25] and commipheric acid was only twice as potent as guggulipid in this assay -a nonsignificant difference in potency. It is possible that myrrhanone A/commipherol [16,17], which is present in guggulipid in a similar amount to commipheric acid (Table 1) and is also a PPARγ agonist [15], made a significant contribution to the PPARγ agonist activity of guggulipid.…”

Synthesis and anticancer activity of novel fused pyrimidine hybrids of myrrhanone C, a bicyclic triterpene of Commiphora mukul gum resin

“…Especially, they accumulate in significant numbers and in abundance in the gum resin of Commiphora mukul (ver: guggul). The major myrrh triterpenes reported from C. mukul are myrrhanones A, B, C and myrrhanols A, B, C [4,5]. Interestingly, these myrrh triterpenes were reported to exhibit significant antiinflammatory and anticancer activities [6][7][8].…”

Plantar Iontophoresis With Aqueous Solution of Guggulu in the Management of Plantar Fascitis: Engendering an Incipient Dimension in Its Management

“…Naringenin: Naringenin is a flavonoid which shows antiinflammatory, antihistaminic, antibacterial and antiviral properties 14 . Myrrhanol A: Myrrhanol A, a triterpene of Commiphora mukul gum resin is recognised as potent anti-inflammatory effects 15 . Myrrhanols B, myrrhanones A, myrrhanones B: These are absolute stereo structures of polypodaneand octanordammarane-type triterpenes with a potent inhibitory effects on nitric oxide production 16 .…”