Guggulu Research Articles

PREVALENCE OF ADVERSE REACTION ALLIED WITH THE USE OF AYURVEDIC MEDICINES FOR ARTHRITIS IN HUMAN POPULATION

Ayurvedic medicine is a system of traditional medicine native to India and a form of alternative medicine. As these drugs are of natural origin, the medical professionals earn a greater financial profit by publicly saying that such drugs are the safest with no adverse effects. But this is not true. As compared to allopathic medicines, ASU (Ayurvedic Siddha Unani) drugs are safe but still these have some potential of causing ADRs. Ayurvedic drugs share a big part in the life of densely populated country like India. As these drugs are of natural origin, the medical professionals earn a greater financial profit by publicly saying that such drugs are the safest with no adverse effects. But this is not true. 50 arthritic patients were given the treatment of Guggul, Alarka, Ashwagandha and Anantmool. In our study it was observed that a total of 67 non serious ADRs had occurred which were urinary burning sensation (23.9%), sleepiness (13.4%), headache (11.9%), nausea (10.5%), nocturia (7.5%), loose stools (7.5%), excessive sweating (6.0%), dizziness (6.0%), polyuria (4.5%), loose motion (3.0%), fatigue (3.0%), flatulence (1.5%) and insomnia (1.5%). From causality assessment it was found that alarka (42%), guggul (33%) and alarka + guggul (25%) were responsible for causing above ADRs. Reported ADRs were evaluated for patient demographics, reaction and drug characteristics, causality, severity, and outcome

Characterization of mode of reproduction in Commiphora wightii [(Arnot) Bhandari] reveals novel pollen–pistil interaction and occurrence of obligate sexual female plants

Guggul [Commiphora wightii (Arnot) Bhandari], a polygamous woody tree valued for its medicinal oleoresin gum rich in guggulsterone, is reported to reproduce via sporophytic apomixis. Details about its natural diversity, and mode and extent of sexual reproduction are, however, scanty. Therefore, a comprehensive investigation of guggul reproduction was made employing histology, controlled pollination, flow cytometry and RAPD analyses of progeny to assess the occurrence and extent of sexual reproduction. We report the discovery of obligate sexual female plants of guggul through these studies. Also, we document a unique pollen–pistil incompatibility that prevents all but one pollen tube growth into the style to effect fertilization. Consequently, obligate sexual female plants produced single-seeded fruit although each flower contains four ovules. In apomictic plants bearing more than one seed per fruit, at most only one seed was of sexual origin. Further, flow cytometric analysis conclusively demonstrated that endosperm development occurs either autonomously or following triple fusion. Autonomous endosperm development was invariably associated with endoreduplication, a unique feature of apomixis in guggul. Despite predominance of apomixis, a low frequency of sexual reproduction was found to persist in apomictic plants yielding new genetic variation. RAPD analysis clearly distinguished accessions and was useful in identifying sexual progenies. The implications of the novel pollen–pistil interaction on establishment and spread of apomixis in guggul are discussed. The study has not only revealed novel features of guggul reproduction but also opened new opportunities for molecular genetic analysis of sporophytic apomixis and breeding improvement of guggul.

Methanol extract of dried exudate of Commiphora mukul prevents bone resorption in ovariectomized rats

Context: Gum guggul, a resinous exudate of the plant Commiphora mukul Engl. (Burseraceae), has been found efficacious in the treatment of bone fractures, arthritis, and hyperlipidemic disorders.Objective: The present study is an effort to explore the anti-bone-resorptive potential of the dried methanol extract of the gummy exudate of C. mukul (MECM) in ovariectomized rat model.Materials and methods: The animals were randomly divided into five groups of equal size (n = 6). Animals in all the groups were ovariectomized except group 1, which was sham operated. Groups 3, 4 and 5 were treated with Raloxifene, MECM 250 mg/kg and MECM 500 mg/kg, respectively. The 2nd group was fed with vehicle. Assessment: biochemical estimations, viz., alkaline phosphatase (ALP), tartarate resistant acid phosphatase (TRAP), serum calcium (Ca); biomechanical evaluations, and histopathological examinations.Results: The LD50 of MECM was found to be > 2500 mg/kg orally. A significant elevation was observed in the ALP, TRAP, Ca and cholesterol levels in the 2nd group with a significant reduction in biomechnical strength. Groups 3, 4 and 5, showed a significant reduction in TRAP and ALP levels (p < 0.001). The Ca levels were normalized in the groups 4 and 5, while cholesterol levels dropped in group 5. The bone strength, however, was normalized in all the groups (p < 0.001) along with the histopathology.Discussion and conclusion: Findings suggested a significant gain in bone strength and nearly complete restoration of bone microarchitecture along with lowered levels of TRAP indicating the anti-bone resorptive potential of the extract.

Promoting Healthy Thyroid Function with Iodine, Bladderwrack, Guggul and Iris

Iodine is an essential component of thyroid hormones and is therefore essential for normal thyroid function. However, the therapeutic use of iodine requires careful evaluation because of its narrow range of intake to support optimal thyroid function. The combination of naturally occurring compounds such as Gum Guggul (Commiphora mukul), Blue Flag root (Iris versicolor) and seaweeds such as Bladderwrack (Fucus vesiculosus) has shown beneficial effects in the treatment of thyroid dysfunction. These compounds have different mechanisms of action and may act synergistically to support thyroid health in conditions such as Hashimoto’s disease and subclinical hypothyroidism.&nbsp;Fucus&nbsp;provides iodine and upregulates the production of iodine-processing hormones, while&nbsp;Commiphora&nbsp;enhances the conversion of T4 to T3, and Iris is a detoxifying agent. These three agents have been used in combination with Nettle leaf (Urtica), Ashwagandha (Withania), Triphala, and Bacopa (Bacopa monnieri), and with supplements supporting basal metabolism and general thyroid function such as L-tyrosine, diiodotyrosine, magnesium, selenium, and iron. Reported side effects include the induction of iodine sensitivity by Bladderwrack and hypersensitivity reactions such as rash and pruritis caused by Guggul. The use of Guggul and Iris is not recommended during pregnancy.

A novel pathovar of Xanthomonas axonopodis causes gumming of Guggal (Commiphora wightii)

Guggal (Commiphora wightii (Arnott) Bhandari comb. nov.) is a small tree which is tapped for medicinally important oleo–gum–resin. Naturally infected plant oozes oleo–gum–resin from its trunk and primary branches. However, in either case, the plant dies slowly after oozing. A bacterium was established to be responsible for these phenomena. Four isolates of this bacterium were characterised by biochemical tests, Biolog GN2 microplate reaction, rDNA sequencing, which suggested that the pathogen belonged to the genus Xanthomonas. However, phylogenetic analysis based on chaperone protein (dnaK) gene, TonB–dependent receptor (fyuA) gene, DNA gyrase B (gyrB) gene and RNA polymerase sigma factor (rpoD) gene sequences placed it as a member of X. axonopodis 9.2 rep–PCR/DNA–DNA homology cluster close to X. perforans, X. alfalfae and X. euvesicatoria. Further elucidation of phylogenetic position of the test strains was achieved from a gyrB based tree considering sequences from 71 representative strains. Test strains were confirmed to be members of X. axonopodis. These had very narrow infectivity limited to Commiphora spp. Hence, we propose a novel pathovar, X. axonopodis pv. commiphoreae pv. nov. as the cause of gum oozing in guggal. Pathotype is DXA 01 = CFBP 7580 = LMG 26789.

Protective effect of ethanolic extract of Commiphora mukul gum resin against oxidative stress in the brain of streptozotocin induced diabetic Wistar male rats.

The objective of the study was to investigate the possible neuroprotective effect of ethanolic extract of Commiphora mukul gum resin (EtCMGR) against oxidative stress in the brain of streptozotocin (STZ) induced diabetic Wistar rats. The experimental animals were divided into four groups: control (C), control treated with EtCMGR (C+CM), diabetic (D) and diabetic treated with EtCMGR (D+CM). Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg body weight). Plant extract treated groups (C+CM and D+CM) were administered EtCMGR at a dose of 200 mg/kg body weight/day by gavage for 60 days. Diabetic rats showed hyperglycemia, hypoinsulinemia with impaired insulin sensitivity. EtCMGR treatment to diabetic (D+CM group) rats prevented the rise in glucose level by 96.7 %, while enhancing insulin level (77.7 %) and improving insulin sensitivity (27.3 %) compared to D group. The brain antioxidant status of D group rats showed higher levels of lipid peroxidation (77.9 %), protein glycation (100 %), and increased activities of xanthine oxidase (47.1 %) and sorbitol dehydrogenase (101.9 %) and lowered concentration of reduced glutathione (38.2 %) and decreased activities of antioxidant enzymes i.e., glutathione reductase (24 %), glutathione peroxidase (24.4 %) and superoxide dismutase (42.1 %) and increased activities of catalase (87.4 %) and glutathione-S-transferase (45.3 %) compared to control group. While EtCMGR treatment for 60 days in D+CM group prevented the observed abnormalities of antioxidant status of D group. This study demonstrates that EtCMGR is a potent neuroprotective agent against oxidative damage induced under diabetes.

Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats

ObjectiveTo study the antioxidant efficacy of Commiphora mukul (C. mukul) gum resin ethanolic extract in streptozotocin (STZ) induced diabetic rats. MethodsThe male Wistar albino rats were randomly divided into four groups of eight animals each: Control group (C), CM-treated control group (C+CMEE), Diabetic control group (D), CM-treated diabetic group (D+CMEE). Diabetes was induced by intraperitoneal injection of STZ (55 mg/kg/bwt). After being confirmed the diabetic rats were treated with C. mukul gum resin ethanolic extract (CMEE) for 60 days. The biochemical estimations like antioxidant, oxidative stress marker enzymes and hepatic marker enzymes of tissues were performed. ResultsThe diabetic rats showed increased level of enzymatic activities aspartate aminotransaminase (AST), alanine aminotransaminase (ALT) in liver and kidney and oxidative markers like lipid peroxidation (LPO) and protein oxidation (PO) in pancreas and heart. Antioxidant enzyme activities were significantly decreased in the pancreas and heart compared to control group. Administration of CMEE (200 mg/kg bw) to diabetic rats for 60 days significantly reversed the above parameters towards normalcy. ConclusionsIn conclusion, our data indicate the preventive role of C. mukul against STZ-induced diabetic oxidative stress; hence this plant could be used as an adjuvant therapy for the prevention and/or management of diabetes and aggravated antioxidant status.

Problems, progress and future prospects of improvement of Commiphora wightii (Arn.) Bhandari, an endangered herbal magic, through modern biotechnological tools: a review

Commiphora wightii (Arn.) Bhandari syn. C. mukul Engl. (Burseraceae) is an economically and pharmacologically important slow growing, dioecious, balsamiferous woody, multipurpose shrub heading towards extinction. Commonly known as “Guggul” due to the presence of steroidal compound guggulsterone in the oleo-gum resin, it has been used in treating various ailments and disorders since ancient times (2000 B.C.). Evaluation and confirmation of hypolipidemic effects of guggul based on Ayurvedic text in 1960s provided a new insight into its pharmacological applications. Two bioactive isomers of guggulsterone, E and Z, are responsible for lipid- and cholesterol-lowering activities. Recently, it has been shown to have anti-cancerous activity also. It is found in the dry regions of Indian subcontinent, namely India, Pakistan and Bangladesh. Ruthless and unscientific harvesting of oleo-gum resin from the wild, by local populations, for economic benefits with negligible conservation efforts has made this species endangered and has led to its inclusion in Red Data Book of IUCN. Although this plant has many excellent traits, adequate attention has not been focused on its conservation and improvement. Conventional propagation methods i.e., seeds, cuttings and air layering are in place but have many limitations. Therefore, application of modern biotechnological tools needs to be standardized for harnessing maximum benefits from this pharmaceutically important plant. An efficient regeneration system needs to be in place for improvement of this genus through genetic transformation and production of useful metabolites in cell cultures. Studies are in progress for micropropagation through shoot multiplication and somatic embryogenesis, as well as for secondary metabolite (guggulsterone) production in callus cultures and bioreactors. No selected germplasm is available for C. wightii since it is a wild plant. Breeding programs have not yet been started due to lack of systematic cultivation and conservation programs. Moreover, little information has been gathered regarding the genetic variability in this species using RAPD and ISSR markers. No details are available about genetic makeup and QTL linkage maps. Investigations are in progress to search sex linked markers in this dioecious species. Research is also in progress to decipher the molecular mechanisms underlying various pharmacological actions of guggul. Since the approval of use of guggul as a food supplement by United States Food and Drug Administration in 1994, an exponential increase in research publications on various aspects of research on guggul have been published. Present communication summarizes the problems, progress made and suggests some future directions of research for this important endangered medicinal plant.

A Review on Bioactive Compounds and Medicinal Uses of Commiphora mukul

A Review on Bioactive Compounds and Medicinal Uses of Commiphora mukul

Steroids from Commiphora mukul display antiproliferative effect against human prostate cancer PC3 cells via induction of apoptosis

Two new stigmastane-type steroids, stigmasta-5,22E-diene-3β,11α-diol (1) and stigmasta-5,22E-diene-3β,7α,11α-triol (2), together with eight known compounds, were isolated from the resinous exudates of Commiphora mukul. Their structures were established by extensive analysis of their HR-MS, 1D- and 2D-NMR (COSY, HMQC, HMBC and NOESY) spectra. The isolates were evaluated for their antiproliferative activities against four human cancer cell lines. Compound 2 demonstrated inhibitory effects with IC50 values of 5.21, 9.04, 10.94 and 16.56μM, respectively, against K562, MCF-7, PC3 and DU145 human cancer cell lines. Further study showed that 2 was able to enforce the PC3 cell cycle arrest in the G2/M phase, and induce the apoptosis of PC3 cells by activation of Bax, caspases 3 and 9, and by inhibition of Bcl-2. It was also found that 1 inhibited proliferation of PC3 cells via G0/G1 phase arrest of the cell cycle.

Antihyperglycemic, hypolipidemic and antioxidant activities of ethanolic extract of Commiphora mukul gum resin in fructose-fed male Wistar rats

High fructose feeding (66 % of fructose) induces type-2 diabetes in rats, which is associated with the insulin resistance, hyperinsulinemia, hypertriglyceridemia and oxidative stress. The present study was undertaken to evaluate the effect of ethanol extract of Commiphora mukul gum resin (CMEE) on blood glucose, plasma insulin, lipid profiles, reduced glutathione, lipid peroxidation, protein oxidation and enzymatic antioxidants like superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase in fructose-induced type-2 diabetic rats. A significant gain in body weight, hyperglycemia, hyperinsulinemia, increased lipid profiles, lipid peroxidation, protein oxidation and decreased reduced glutathione, activities of enzymatic antioxidants and insulin sensitivity (increased homeostasis assessment assay) were observed in high-fructose-induced diabetic rats. The administration of CMEE (200 mg/kg/day) daily for 60 days in high-fructose-induced diabetic rats reversed the above parameters significantly. CMEE has the ability to improve insulin sensitivity and delay the development of insulin resistance, aggravate antioxidant status in diabetic rats and may be used as an adjuvant therapy for patients with insulin resistance.

Pharmacological Properties of Guggulsterones, the Major Active Components of Gum Guggul

Oleo gum resin secreted by Commiphora mukul, also known as gum guggul, has been used widely as an ayurvedic drug. Commiphora mukul is a short thorny shrub that is native to the Indian subcontinent. Oleo gum resin extracted by incision of the bark is a very complex mixture of gum, minerals, essential oils, terpenes, sterols, ferrulates, flavanones and sterones. Its active constituents, the Z- and E-guggulsterones, have been demonstrated to exhibit their biological activities by binding to nuclear receptors and modulating the expression of proteins involved in carcinogenic activities. Guggulsterones have also been reported to regulate gene expression by exhibiting control over other molecular targets including transcription factors such as nuclear factor (NF)-κB, signal transducer and activator of transcription (STAT) and steroid receptors. Considerable scientific evidence indicates the use of gum guggul as a therapeutic agent in the treatment of inflammation, nervous disorders, hyperlipidaemia and associated cardiac disorders such as hypertension and ischaemia, skin disorders, cancer and urinary disorders. This review highlights the taxonomic details, phytochemical properties and pharmacological profile of gum guggul.

Morphological characterization of guggal (Commiphora wightii) provenances from extremely arid parts of India

Commiphora wightii is one of the major guggal gum-resin producing species in India. It has never been brought under cultivation and the species is now considered endangered. Growth performances and morphological parameters were assessed during 2008 and 2009 at Jaisalmer, in the hyper arid part of India, for five provenances of Commiphora wightii, viz., Dantiwara, Mangaliawas, Kukma-Bhuj, Bhind-Murena, and Jaisalmer local. Observations revealed a significant amount of variation for plant height, stem girth, number of branches per plant, crown spread, leaflet shape, and 100 seed weight. The provenances have shown measurable growth responses, which were sufficient for a conclusive remark. Such variation among different populations may be due to different intensities of natural selection acting upon the traits in their natural habitat. Results of this study are important for the conservation of the genetic variation of the species and for future improvement schemes: they indicate that genetic differences exist among provenances of guggal (Commiphora wightii), with Jaisalmer local, Mangaliawas, and Dantiwara showing satisfactory performance for cultivation in arid parts of India.

Gugulipid, an Extract of Ayurveda Medicine Plant Commiphora Mukul as a Potent Agent for Cancer Chemoprevention and Cancer Chemotherapy

Gugulipid (GL), an extract of Commiphora mukul, has been safely used for thousands of years in the Indian Ayurveda medicine practice for the treatment of different ailments and has been used recently in many clinical trials that focused on its cholesterol-lowering effect. GL has recently been paid great attention for its cancer chemopreventive and chemotherapeutic potential. Z- and E-Guggulsterone have been identified as the major active components of GL. Studies have shown that GL as well as Guggulsterones can inhibit cancer growth in vitro and in vivo and lead to prevention of cancer initiation, promotion and progression. Although the action mechanisms of GL are not completely understood, GL has been revealed as a multitargeted cancer chemopreventive and chemotherapeutic agent. The increased understanding of the anti-cancer activity of GL and its molecular targets would allow us to improve its efficacies in different types of human cancers by single and/or combination strategies.

Comparative study of hypolipidemic profile of resinoids of Commiphora mukul/Commiphora wightii from different geographical locations

The antihyperlipidemic activity of resinoids of guggul (Commiphora mukul/Commiphora wightii), belonging to family Burseraceae (Genus: Commiphora), collected from different parts of India (Gujarat, Madhya Pradesh and Rajasthan), was studied on cholesterol-rich high fat diet-induced model of hyperlipidemia in rats. The resinoids of these exudates were prepared in ethyl acetate and ethyl alcohol. The physicochemical characterization of these resinoids was carried out to determine their appearance, %yield, %moisture, %ash, acid value (mg/KOH/g), saponification value (mg/KOH/g), ester value and iodine value (g/g). Antihyperlipidemic study was carried out on all resinoids in high fat diet induced model of hyperlipidemia in Wistar albino rats. The result demonstrated that the resinoids of exudates of Commiphora wightii and Commiphora mukul, collected from Gujarat and extracted in ethyl acetate, and the resinoids of exudates of Commiphora mukul, collected from Madhya Pradesh and extracted in ethyl acetate, possessed significantly higher antihyperlipidemic activity compared with other resinoids, which may be due to regional/geographical variations.

Synergistic effect of Commiphora mukul (gum resin) and Lagenaria siceraria (fruit) extracts in high fat diet induced obese rats

ObjectiveTo investigate the synergistic effect of Commiphora mukul (gum resin) and Lagenaria siceraria (fruit) extracts in high fat diet induced obese rats. MethodsRats were randomly divided into seven groups: (i) non-obese control (NOB), (ii) Obese control (OB), (iii) orlistat (50 mg/kg; p.o.), (iv) ethyl acetate extract of Commiphora mukul (gum resin) (200 mg/kg; p.o.), (v) ethanolic extract of Lagenaria siceraria (fruit) (200 mg/kg; p.o.) were examined individually, (vi) C. mukul and L.siceraria (200 mg/kg; p.o.) and (vii) C. mukul and L.siceraria (400 mg/kg; p.o.)extracts were administered in combination to the high fat-diet-induced obese rats for 30 days to evaluate its synergistic activity. ResultsFor synergistic effect, after combination treatment caused most significant (P < 0.001) reduction in body weight, fasting blood glucose, serum levels of cholesterol, triglyceride, LDL, VLDL and increase levels of HDL. ConclusionsThe result demonstrated that combination C.mukul and L.siceraria has ameliorated the high fat diet induced obesity.

Protective and restorative effects of a Commiphora mukul gum resin and triheptanoin preparation on the CCL‐110 skin fibroblast cell line

Coenzyme Q10 (CoQ10) is a major ingredient in skin care products because of its anti-wrinkle effects, although it has some side effects especially at higher amounts. In this study, we compare the anti-wrinkle related properties of CoQ10 and a proprietary Commiphora mukul gum resin (guggul) and triheptanoin preparation (GU-TC7). GU-TC7 is prepared with a supercritical CO₂-co-solvent extraction with ethanol, standardized to 2% guggulsterones and triheptanoin, a triglyceride composed of three 7-carbon fatty acids. Treatment of CCL-110 skin fibroblasts with GU-TC7 demonstrates a mild proliferative effect compared to CoQ10 and increased type I collagen synthesis. Additionally, GU-TC7 inhibited matrix metalloproteinase-1 (MMP-1) expression in a dose-dependent manner at 20-100 μg mL⁻¹ and inhibited human elastase expression by more than 50% as compared to no elastase inhibition with CoQ10 treatment. These results suggest that GU-TC7 possesses properties that are applicable to the treatment of wrinkles and may be considered for its further evaluation in skin care products.

In vitro propagation of endangered medicinal plant–Commiphora wightii

Present study reports in vitro multiplication and conservation of Commiphora wightii and the influence of growth regulators, location of the explant on mother plant, influence of apical dominance and the size of explant on regeneration ability. Out of the 40, single as well as combinations of BAP, Kn, NAA, IBA and GA3 used, only three combination treatments of BAP (3mg/l) with IBA (0.1-0.3mg/l) induced shoot development in node and shoot tip cultures. Further, among the three nodes, 1st node (shoot tip) performed better on BAP, IBA and GA3 supplemented medium. Commiphora wightii shows strong apical dominance, the influence of dominance was tested with four explants- shoot tip, simple node, axillary bud and node –AD. Shoot tip, simple node, and axillary bud result no shoot bud development on any concentration or combinations of BAP and/or GA3 tested. Whereas, the node -ADs alone showed shoots development. Best percentage response of node-AD was observed on 2mg/l BAP+0.5mg/l GA3 (27%) followed by 1mg/l BAP+1.5mg/l GA3 (25%) medium. Further, node-AD with two nodes and two internodes performed better and survived for more than 6 weeks on the same medium without subculture as compared to node-AD of 0.5-0.8 cm in size with single node. Regenerated shoots transferred to MS + activated charcoal medium after dipping in NAA, IAA or IBA (200ppm) solutions , showed root development within 20 days of culture with 24 – 26% response. All the regenerated plants were successfully transferred to field conditions. Thus, the paper reports the successful in vitro propagation of Commiphora wightii. Keywords: Commiphora wightii, Endangered, Medicinal plant, In vitro propagation, Tissue culture, India

Guggulsterone induces heme oxygenase-1 expression through activation of Nrf2 in human mammary epithelial cells: PTEN as a putative target

Guggulsterone (GS) [4,17(20)-pregnadiene-3,16-dione] is a phytosterol found in the gum resin of the Commiphora mukul. GS exists naturally in two stereoisomers: E-GS (cis-GS) and Z-GS (trans-GS). In this study, the effects of both isomers on expression of the cytoprotective enzyme heme oxygenase-1 (HO-1) were evaluated in human mammary epithelial (MCF10A) cells. NF-E2-related factor 2 (Nrf2) is considered a master regulator in activating antioxidant response element (ARE)-driven expression of HO-1 and many other antioxidant/cytoprotective proteins. cis-GS upregulated the transcription and protein expression of HO-1 to a greater extent than did trans-GS. cis-GS treatment enhanced nuclear translocation and ARE-binding activity of Nrf2. MCF10A cells transfected with an ARE luciferase construct exhibited significantly elevated Nrf2 transcriptional activity upon cis-GS treatment compared with cells transfected with the control vector. In addition, silencing of the Nrf2 gene abrogated cis-GS-induced expression of HO-1. Incubation of MCF10A cells with cis-GS increased phosphorylation of Akt. The pharmacological inhibition of phosphoinositide 3-kinase (PI3K), an upstream kinase responsible for Akt phosphorylation, abrogated cis-GS-induced Nrf2 nuclear translocation. Pretreatment with the thiol-reducing agents attenuated Akt phosphorylation, Nrf2 activation and HO-1 expression, suggesting that cis-GS may cause thiol modification of an upstream signaling modulator. Phosphatase and Tensin Homologue Deleted on Chromosome 10 (PTEN) is a negative regulator of the PI3K-Akt axis. The mutation in cysteine 124 present in the catalytic domain of PTEN abolished cis-GS-induced HO-1 expression as well as Akt phosphorylation. Whether this cysteine is a 'bona fide' target of cis-GS in its activation of Nrf2 needs additional investigation.

SCREENING OF E- AND Z-GUGGULSTERONES IN THE GUM-RESIN EXUDATES OF SOME COMMON PLANTS AND METHOD VALIDATION IN RAW, EXTRACTED, AND PHARMACEUTICAL FORMULATIONS OF COMMIPHORA MUKUL BY HPLC

Hypolipidemic agents, E- and Z-guggulsterones, are the biomarker compounds found in the gum-resin exudates of Commiphora mukul. Gum-Resin exudates of six common plants included Mangifera indica, Ficus religiosa, Delonix regia, Acacia nilotica, Abies balsamea, and Commiphora stocksiana and were screened against the said drug by the HPLC method. The developed method was validated for the quantification of E- and Z-guggulsterones in the gum-resin exudates of Commiphora mukul (raw form), guggulipid (ethyl acetate extract of gum-resin,) and its pharmaceutical products (finished form) that are the various components involved in the preparation of pharmaceutical products, from raw materials to finished products. The method involved a simple extraction procedure under sonication. The new method was validated as per the ICH recommended guidelines, including specificity, linearity, precision, accuracy, limit of quantitation, and robustness. The method has a validated quantitation range of 2–65 µg/mL with a precision of ±2% SD, recovery of >99.5% and correlation coefficients >0.999 for both E- and Z-guggulsterones. The statistical analysis proves that the method is repeatable and selective for the estimation of the said drugs and can be used as a routine analytical method and applicable to the different processing components involved in the pharmaceutical preparation from Commiphora mukul resin. Supplemental materials are available for this article. Go to the publisher's online edition of the Journal of Liquid Chromatograhy & Related Technologies to view the free supplemental file.