Download PDF
Planta Med 2019; 85(16): 1225-1232
DOI: 10.1055/a-1014-3303
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Virucidal Effect of Guggulsterone Isolated from Commiphora gileadensis

Lamjed Bouslama
1   Laboratory of Bioactive Substances, Center of Biotechnology of Borj Cedria, University of Tunis El Manar, Tunisia
,
Bochra Kouidhi
2   Medical Laboratory Department, College of Applied Medical Sciences, Yanbu, Taibah University, Saudi Arabia
,
Yasir Mohammed Alqurashi
2   Medical Laboratory Department, College of Applied Medical Sciences, Yanbu, Taibah University, Saudi Arabia
,
Kamel Chaieb
3   Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
4   Laboratory of Analysis, Treatment and valorization of Pollutants of the Environment and Products, Faculty of Pharmacy, Monastir University, Tunisia
,
Adele Papetti
5   Nutraceutical & Food Chemical-Toxicological Analysis Laboratory, Department of Drug Sciences, University of Pavia, Italy
› Author Affiliations
Further Information

Publication History

received 22 May 2019
revised 12 September 2019

accepted 12 September 2019

Publication Date:
07 October 2019 (online)

   Permissions and Reprints

Abstract

Commiphora gileadensis, locally known as becham, is a plant used in traditional Arabian medicine for treating headache, constipation, stomach, joint pain, and inflammatory disorders. Several studies have reported its antibacterial properties; however, no study has demonstrated its antiviral activity. This study aimed to evaluate the antiviral activity of C. gileadensis as well as to isolate its active compound and investigate its mode of action. This activity was evaluated using 4 viruses, herpes simplex virus type 2 (HSV-2), respiratory syncytial virus type B (RSV-B), coxsackie virus B type 3, and adenovirus type 5 by performing the plaque reduction assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for enveloped and nonenveloped viruses, respectively. The methanol extract of C. gileadensis leaves only showed antiviral activity against enveloped viruses with a selectivity index of 11.19 and 10.25 for HSV-2 and RSV-B, respectively. The study of the mechanism underlying antiviral activity demonstrated a virucidal effect by direct contact with these target viruses. The active compound, isolated using bio-guided assays involving TLC, was identified as guggulsterone by HPLC-diode array detection coupled with electrospray ionization mass spectrometry. Guggulsterone is an antagonist of the bile acid receptor and a modulator of cholesterol metabolism; however, its antimicrobial properties have been reported for the first time in this study.

Key words

Burseraceae - Commiphora gileadensis - cytotoxicity - herpes simplex virus type 2 - respiratory syncytial virus type B - virucidal activity - guggulsterone
 

  • References

  • 1 Chaudhary SA, Al-Jowaid AA. Vegetation of the Kingdom of Saudi Arabia. Riyadh: National Agriculture & Water Research Center; 1999
    Google Scholar
  • 2 Hepper FN, Friis I. The Plants of Pehr Forsskalʼs Flora Aegyptiaco Arabiea. Kew: Royal Botanic Gardens; 1994: 1761-1763
    Google Scholar
  • 3 Miller AG, Morris M. Plants of Dhofar: the southern Region of Oman, traditional, economic and medicinal Uses. Oman: Office of the Adviser for Conservation of the Environment, Diwan of Royal Court Sultanate of Oman; 1988
    Google Scholar
  • 4 Migahid AM. Flora of Saudi Arabia, vol. 2. Riyadh: Riyadh University Publications; 1978: 647
    Google Scholar
  • 5 Al-Aklabi A, Al-Khulaidi AW, Hussain A, Al-Sagheer N. Main vegetation types and plant species diversity along an altitudinal gradient of Al Baha region, Saudi Arabia. Saudi J Biol Sci 2016; 23: 687-697
    CrossrefPubMedGoogle Scholar
  • 6 Roweha A. Al-Tadawi Bel-Aʼashab (Plant Therapy). Beirut: Al-Andalus Press; 1983: 170-172
    Google Scholar
  • 7 Al-Howiriny T, Al-Sohaibani M, Al-Said M, El-Tahir K, Rafatullah S. Hepatoprotective properties of Commiphora opobalsamum (“Balessan”), a traditional medicinal plant of Saudi Arabia. Drugs Exp Clin Res 2004; 30: 213-220
    PubMedGoogle Scholar
  • 8 Al-Yahya MA, Al-Meshal IAR, Mossa JS, Al-Badr AA, Tariq M. Saudi Plants: Phytochemical and Biological Approach. KASCT No 39. Riyadh: King Saud University Press; 1990
    Google Scholar
  • 9 Abdul-Ghani AS, Amin R. Effect of aqueous extract of Commiphora opobalsamum on blood pressure and heart rate in rats. J Ethnopharmacol 1997; 57: 219-222
    CrossrefPubMedGoogle Scholar
  • 10 Al-Howiriny T, Al-Sohaibani M, Al-Said M, Al-Yahya M, El-Tahir K, Rafatullah S. Effect of Commiphora opobalsamum (L.) Engl. (Balessan) on experimental gastric ulcers and secretion in rats. J Ethnopharmacol 2005; 98: 287-294
    CrossrefPubMedGoogle Scholar
  • 11 Wineman E, Douglas I, Wineman V, Sharova K, Jaspars M, Meshner S, Bentwich Z, Cohen G, Shtevi A. Commiphora gileadensis sap extract induces cell cycle-dependent death in immortalized keratinocytes and human dermoid carcinoma cells. J Herb Med 2015; 5: 199-206
    CrossrefPubMedGoogle Scholar
  • 12 Abbas FA, Al-Massarany SM, Khan S, Al-Howiriny TA, Mossa JS, Abourashed EA. Phytochemical and biological studies on Saudi Commiphora opobalsamum L. Nat Prod Res 2007; 21: 383-391
    CrossrefPubMedGoogle Scholar
  • 13 Orchard A, Sandasi M, Kamatou G, Viljoen A, van Vuuren SF. The in vitro antimicrobial activity and chemometric modelling of 59 commercial essential oils against pathogens of dermatological relevance. Chem Biodivers 2017; 14: e1600218
    CrossrefPubMedGoogle Scholar
  • 14 Lee K, Lee JH, Kim SI, Cho MH, Lee J. Anti-biofilm, anti-hemolysis, and anti-virulence activities of black pepper, cananga, myrrh oils, and nerolidol against Staphylococcus aureus . Appl Microbiol Biotechnol 2014; 98: 9447-9457
    CrossrefPubMedGoogle Scholar
  • 15 Al-Sieni AI. The antibacterial activity of traditionally used Salvadora persica L.(miswak) and Commiphora gileadensis (palsam) in Saudi Arabia. Afr J Tradit Complement Altern Med 2014; 11: 23-27
    PubMedGoogle Scholar
  • 16 Bhatta RS, Kumar D, Chhonker YS, Jain GK. Simultaneous estimation of E- and Z-isomers of guggulsterone in rabbit plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study. Biomed Chromatogr 2011; 25: 1054-1060
    CrossrefPubMedGoogle Scholar
  • 17 Bakari GG, Max RA, Mdegela RH, Phiri EC, Mtambo MM. Antiviral activity of crude extracts from Commiphora swynnertonii against Newcastle disease virus in ovo . Trop Anim Health Prod 2012; 44: 1389-1393
    CrossrefPubMedGoogle Scholar
  • 18 Hussein G, Miyashiro H, Nakamura N, Hattori M, Kakiuchi N, Shimotohno K. Inhibitory effects of Sudanese medicinal plant extracts on hepatitis C virus (HCV) protease. Phytother Res 2000; 14: 510-516
    CrossrefPubMedGoogle Scholar
  • 19 Mothana RA, Mentel R, Reiss C, Lindequist U. Phytochemical screening and antiviral activity of some medicinal plants from the island Soqotra. Phytother Res 2006; 20: 298-302
    CrossrefPubMedGoogle Scholar
  • 20 Cenci E, Messina F, Rossi E, Epifano F, Marcotullio MC. Antiviral furanosesquiterpenes from Commiphora erythraea . Nat Prod Commun 2012; 7: 143-144
    PubMedGoogle Scholar
  • 21 Haque I, Kumar M, Mukhopadhyay K. A rapid and simple UPLC-MS-MS based simultaneous determination of the medicinally important E- and Z-guggulsterone from oleogum-resins of naturally occurring Commiphora wightii plants. Chromatographia 2009; 70: 1613-1619
    CrossrefPubMedGoogle Scholar
  • 22 Musharraf SG, Iqbal N, Gulzar U, Ali A, Choudhary MI. Atta-Ur-Rahman. Effective separation and analysis of E- and Z-guggulsterones in Commiphora mukul resin, guggulipid and their pharmaceutical product by high performance thin-layer chromatography-densitometric method. J Pharm Biomed Anal 2011; 56: 240-245
    CrossrefPubMedGoogle Scholar
  • 23 Nityanand S, Srivastava JS, Asthana OP. Clinical trials with gugulipid. A new hypolipidaemic agent. J Assoc Physicians India 1989; 37: 323-328
    PubMedGoogle Scholar
  • 24 Singh RB, Niaz MA, Ghosh S. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 1994; 8: 659-664
    CrossrefPubMedGoogle Scholar
  • 25 Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, DerMarderosian AH, Cirigliano MD, Rader DJ. Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. JAMA 2003; 290: 765-772
    CrossrefPubMedGoogle Scholar
  • 26 Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 2002; 296: 1703-1706
    CrossrefPubMedGoogle Scholar
  • 27 Wu J, Xia C, Meier J, Li S, Hu X, Lala DS. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol 2002; 16: 1590-1597
    CrossrefPubMedGoogle Scholar
  • 28 Cui J, Huang L, Zhao A, Lew JL, Yu J, Sahoo S, Meinke PT, Royo I, Peláez F, Wright SD. Guggulsterone is an farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem 2003; 278: 10214-10220
    CrossrefPubMedGoogle Scholar
  • 29 Owsley E, Chiang JY. Guggulsterone antagonizes farnesoid X receptor induction of bile salt export pump but activates pregnane X receptor to inhibit cholesterol 7alpha-hydroxylase gene. Biochem Biophys Res Commun 2003; 304: 191-195
    CrossrefPubMedGoogle Scholar
  • 30 Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, Krishnan V, Bullock HA, Burris LL, Galvin RJ, Bramlett K, Stayrook KR. The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol 2005; 67: 948-954
    CrossrefPubMedGoogle Scholar
  • 31 Shishodia S, Aggarwal BB. Guggulsterone inhibits NF-κB and IκBα kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. J Biol Chem 2004; 279: 47148-47158
    CrossrefPubMedGoogle Scholar
  • 32 Aggarwal BB. Nuclear factor-κB: the enemy within. Cancer Cell 2004; 6: 203-208
    CrossrefPubMedGoogle Scholar
  • 33 Beg AA, Baltimore D. An essential role for NF-κB in preventing TNF-α-induced cell death. Science 1996; 274: 782-784
    CrossrefPubMedGoogle Scholar
  • 34 Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM. Suppression of TNF-α-induced apoptosis by NF-κB. Science 1996; 274: 787-789
    CrossrefPubMedGoogle Scholar
  • 35 Baeuerle PA, Henkel T. Function and activation of NF-kappaB in the immune system. Annu Rev Immunol 1994; 12: 141-179
    CrossrefPubMedGoogle Scholar
  • 36 Lv N, Song MY, Kim EK, Park JW, Kwon KB, Park BH. Guggulsterone, a plant sterol, inhibits NF-κB activation and protects pancreatic β cells from cytokine toxicity. Mol Cell Endocrinol 2008; 289: 49-59
    CrossrefPubMedGoogle Scholar
  • 37 Verma N, Singh SK, Gupta RC. Pharmacokinetics of guggulsterone after intravenous and oral administration in rats. Pharma Pharmacol Commun 1999; 5: 349-354
    PubMedGoogle Scholar
  • 38 Sudo K, Konno K, Yokota T, Shigeta S. A sensitive assay system screening antiviral compounds against herpes simplex virus type 1 and type 2. J Virol Methods 1994; 49: 169-178
    CrossrefPubMedGoogle Scholar
  • 39 Reed L, Muench H. A simple method of estimating fifty pet cent endpoints. Am J Epidemiol 1938; 27: 493-497
    CrossrefPubMedGoogle Scholar
  • 40 Hayashi K, Hayashi T, Morita N. Mechanism of action of the antiherpesvirus biflavone ginkgetin. Antimicrob Agents Chemother 1992; 36: 1890-1893
    CrossrefPubMedGoogle Scholar
  • 41 Guo JP, Pang J, Wang XW, Shen ZQ, Jin M, Li JW. In vitro screening of traditionally used medicinal plants in China against enteroviruses. World J Gastroenterol 2006; 12: 4078-4081
    CrossrefPubMedGoogle Scholar