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The Therapeutic Potential of the Labdane Diterpenoid Forskolin

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The Therapeutic Potential of the Labdane Diterpenoid Forskolin applied sciences Review The Therapeutic Potential of the Labdane Diterpenoid Forskolin Bahare Salehi 1 , Mariola Staniak 2 , Katarzyna Czopek 2 , Anna St˛epie´n 2 , Kamal Dua 3,4,5,*, Ridhima Wadhwa 6, Dinesh Kumar Chellappan 7, Oksana Sytar 8,9 , Marian Brestic 9 , Namrata Ganesh Bhat 10, Nanjangud Venkatesh Anil Kumar 10 , María del Mar Contreras 11,* , Farukh Sharopov 12,* , William C. Cho 13,* and Javad Sharifi-Rad 14,* 1 Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam 44340847, Iran; [email protected] 2 Institute of Soil Science and Plant Cultivation—State Research Institute, Czartoryskich Str. 8, 24-100 Puławy, Poland; [email protected] (M.S.); [email protected] (K.C.); [email protected] (A.S.) 3 Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia 4 Centre for Inflammation, Centenary Institute, University of Newcastle, Callaghan, NSW 2308, Australia 5 Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia 6 Faculty of Life Science and Biotechnology, South Asian University, Akbar Bhawan, Chanakyapuri, New Delhi 110021, India; [email protected] 7 Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia; [email protected] 8 Department of Plant Biology Department, Taras Shevchenko National University of Kyiv, Institute of Biology, Volodymyrska str., 64, Kyiv 01033, Ukraine; [email protected] 9 Department of Plant Physiology, Slovak University of Agriculture, Nitra, A. Hlinku 2, 94976 Nitra, Slovak; [email protected] 10 Department of Chemistry, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal 576104, India; [email protected] (N.G.B.); [email protected] (N.V.A.K.) 11 Department of Chemical, Environmental and Materials Engineering, University of Jaén, 23071 Jaén, Spain 12 Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Dushanbe 73400, Tajikistan 13 Department of Clinical Oncology, Queen Elizabeth Hospital, 30 Gascoigne Road, Hong Kong, China 14 Department of Pharmacology, Faculty of Medicine, Jiroft University of Medical Sciences, Jiroft 7861756447, Iran * Correspondence: [email protected] (K.D.); [email protected] or [email protected] (M.d.M.C.); [email protected] (F.S.); [email protected] (W.C.C.); javad.sharifi[email protected] (J.S.-R.) Received: 30 August 2019; Accepted: 26 September 2019; Published: 30 September 2019 Abstract: Forskolin is mainly found in the root of a plant called Coleus forskohlii (Willd.) Briq., which has been used in the traditional medicine of Indian Ayurvedic and Southeast Asia since ancient times. Forskolin is responsible for the pharmacological activity of this species. Forskolin is a labdane diterpenoid with a wide biological effect. Several studies suggested a positive role of forskolin on heart complications, respiratory disorders, high blood pressure, obesity, and asthma. There are numerous clinical and pre-clinical studies representing the effect of forskolin on the above-mentioned disorders but more clinical studies need to be performed to support its efficacy. Keywords: forskolin; plant secondary metabolites; Coleus forskohlii; cAMP pathway Appl. Sci. 2019, 9, 4089; doi:10.3390/app9194089 www.mdpi.com/journal/applsci Appl.Appl. Sci. Sci. 20192019, ,99, ,x 4089 FOR PEER REVIEW 22 of of 13 13 1. Introduction 1. Introduction The fortitude of traditional medicine depends on the knowledge of plant medicinal characteristics.The fortitude The of major traditional drivers medicine of the depends pharmacological on the knowledge actions ofof plant medicinal medicinal plants characteristics. are plant secondaryThe major metabolites drivers of [1,2] the. pharmacologicalSecondary metabolites actions are of medicinalknown as plantssignal aremolecules plant secondaryfor plant biosynthesismetabolites [1but,2] .also Secondary play defense metabolites role areagai knownnst herbivores, as signal moleculesand other for plants plant and biosynthesis microbes but [3– also5]. Terpenesplay defense are rolea diverse against and herbivores, big group and of organic other plants compounds, and microbes which [ 3are–5]. present Terpenes in medicinal are a diverse plants and andbig groupmay protect of organic the plants compounds, that produce which arethem present by deterring in medicinal herbiv plantsores and and by may attracting protect predators the plants andthat produceparasites them of herbivores by deterring [6] herbivores. The treatment and by attractingof health predatorsdisorders and and parasites infections of herbivoreswith herbal [6]. medicinesThe treatment engages of health active disorders natural and products infections, mostly with herbalof low medicinesmolecular engages weight, active with naturalgreat structural products, diversitymostly of such low molecularas terpenes weight, and terpenoids with great [7,8] structural. diversity such as terpenes and terpenoids [7,8]. TerpenesTerpenes and and terpenoids terpenoids are are the the main main components components of of the the essential essential oils oils of of many many types types of of plants plants andand flowers. flowers. Their Their biosynthesis biosynthesis occurs occurs within within specific specific tissues tissues or or at at specific specific stages stages of of development development in in plantsplants [9] [9].. Many Many terpenoids terpenoids also also possess possess pharmaceutical pharmaceutical properties properties and and are are currently currently being being used used in in clinicalclinical practices. practices. Nowadays Nowadays,, terpenoids terpenoids intensively intensively applied applied in in traditional traditional drugs drugs are are taxol taxol (diterpene) (diterpene) fromfrom TaxusTaxus b baccataaccata L. and artemisinin (sesq (sesquiterpeneuiterpene lactone) lactone) from from ArtemisiaArtemisia annua annua L.L. as as malaria malaria and and cancercancer medicines medicines,, respectively, respectively, and forskolin (Figure 11a)a) fromfrom ColeusColeus forskohliiforskohlii (Willd.)(Willd.) Briq. (also (also knownknown as as PlectranthusPlectranthus forskohlii forskohlii Willd.)Willd.) (Lamiaceae) (Lamiaceae) [10 [10––1313]].. Forskolin Forskolin is is known known to to treat treat conditions conditions suchsuch as as heart heart complications, complications, respiratory respiratory disorders, and asthma [14,15] [14,15].. (a) (b) (c) FigureFigure 1. 1. TheThe chemical chemical structure structure of of:: (a (a) )forskolin forskolin;; (b (b) )geranyl geranyl geranyl geranyl diphosphate diphosphate;; a andnd ( (cc)) 13R 13R-manoyl-manoyl oxideoxide.. InIn particular, particular, forskolin forskolin,, which which is is exclusively exclusively found found in in the the root root of of CC.. forskohlii forskohlii,, has has been been used used in in traditionaltraditional IndianIndian Ayurvedic,Ayurvedic under, under the the name name “Makandi” “Makandi” or “Mayani”, or “Mayani”, and Southeast and South Asianeast medicine Asian medicinesince ancient since times ancient [15 times]. In African[15]. In African countries, countries it is commonly, it is commonly known known as a drug as a in drug diseases in diseases of the ofdigestive, the digestive, urinary urinary and respiratory and respiratory tracts [16 tract]. C.s [ forskohlii16]. C. forskohliiis commonly is commonly found in found Nepal, in Burma, Nepal, Thailand, Burma, Thailandand India., and It isIndia. also grownIt is also in manygrown East in many African East countries African [ 16countries–18]. India [16– is18 a]. leadingIndia is exporter a leading of exporterC. forskohlii of extractsC. forskohlii and itsextracts products and to its various products countries, to various mainly countries, USA, Poland, mainly South USA, Korea, Poland, Australia, South Korea,Japan, Australia, Italy, Spain, Japan, South Italy, Africa, Spain, and South Canada Africa [19]., and Chemically, Canada [ the19]. wholeChemically, plant isthe rich whole in alkaloids, plant is richbut thein alkaloids, most desirable but the part most of desirable the plant part is the of roots,the plant because is the they roots, contain because the they highest contain concentrations the highest concentrations of forskolin. In the extracts obtained from the C. forskohlii, the presence of α-amyrin, Appl. Sci. 2019, 9, 4089 3 of 13 of forskolin. In the extracts obtained from the C. forskohlii, the presence of α-amyrin, β-sitosterol, betulinic acid, α-cedrol, citronellal and α-cedren was also identified. Other diterpenoids such as forskoditerpenoside A and B were also detected in the ethanolic extract from C. forskohlii, while in the essentialAppl. oil Sci. obtained 2019, 9, x FOR from PEER the REVIEW roots of the plant were identified, among others: borneol, α-humulene,3 of 13 α β α 1-octadecanol,β-sitosterol, 1-decanol, betulinic acid, decanoic α-cedrol, acid, citronellal 4-terpineol, and α 1,8-cineol,-cedren was also- and identified.-pinene, Other camphene, diterpenoids-cedrol, α-ylangene,such as andforskoditerpenosideγ-terpinene [15 A,16 and,18 B]. were However, also detected the latter in the compounds ethanolic extract have from a weaker C. forskohlii therapeutic, effect comparedwhile in the toessential forskolin. oil obtained Hence, from the researchthe roots resultsof the plant show were that identified
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