Plectranthus Barbatus: a Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2

Reviews 753 Plectranthus barbatus: A Review of Phytochemistry, Ethnobotanical Uses and Pharmacology – Part 2 Authors Rawiya H. Alasbahi 1, Matthias F. Melzig 2 Affiliations 1 Faculty of Pharmacy, Department of Pharmacognosy, University of Aden, Crater-Aden, Yemen 2 Institute of Pharmacy, Free University Berlin, Berlin, Germany Key words Abstract liver fatigue, respiratory disorders, heart diseases l" Plectranthus barbatus ! and certain nervous system disorders. Forskolin l" Lamiaceae Plectranthus barbatus Andr. is one of the most im- as one of the major constituents with its unique l" forskolin portant species of the genus Plectranthus L′ Herit. adenylyl cyclase activation that underlies the l" phytochemistry (Lamiaceae), with a wide variety of traditional wide range of pharmacological properties could l" ethnobotanical uses l" pharmacology medicinal uses in Hindu and Ayurvedic tradition- explain the different traditional uses of Plectran- l" 6‑(3‑dimethylaminopropio- al medicine as well as in the folk medicine of Bra- thus barbatus. Forskolin is involved in a number nyl)forskolin hydrochloride zil, tropical Africa and China. The plant has there- of patented pharmaceutical preparations used as (NKH477) fore been an attractive target for intensive chem- over-the-counter drugs for the treatment of sev- ical and pharmacological studies up to now. This eral ailments. However, the water-insoluble na- review presents data about the phytochemistry, ture of forskolin limits its clinical usefulness. For- ethnobotanical uses and pharmacology of Plec- skolin thus served as a prototype for the develop- tranthus barbatus as well as the pharmacology of ment of 6-(3-dimethylaminopropionyl)forskolin its constituents. In addition to essential oil, abie- hydrochloride (NKH477) as a potent water-solu- tane diterpenoids and 8,13-epoxy-labd-14-en- ble forskolin derivative that finds use in the ther- 11-one diterpenoids are the main constituents apy for a number of diseases especially of the car- found in Plectranthus barbatus. The major ethno- diovascular system. botanical uses are for intestinal disturbance and Pharmacology anti-implantation and, after embryo implanta- ! tion, a delay in the development associated with Plectranthus barbatus maternal toxicity [12]. The water extract of P. bar- received May 19, 2009 Studies on several extracts with various polarities batus leaves was found to exert hypoglycemic, revised Dec. 8, 2009 obtained from different parts of P. barbatus re- hypotensive and antispasmodic activities [13]. It accepted January 25, 2010 vealed a number of pharmacological properties has been demonstrated that the water extract This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. Bibliography that may justify most of the traditional uses of P. (WE) of the stems and leaves, at a dose of 1 g/kg DOI http://dx.doi.org/ barbatus, for example, organic extracts were re- p.o., shortened the sleeping time induced by pen- 10.1055/s-0029-1240919 ported to possess anti-inflammatory, antimicro- tobarbital by 37%, and at a dose of 2 g/kg p.o. en- Published online February 25, bial [1,2], antioxidant [3], cytotoxic [4], hypoten- hanced the intestinal transit of charcoal by 30% in 2010 sive [5,6], spasmolytic [7], hepatoprotective [8] mice. The WE (2 g/kg/intraduodenal) also re- Planta Med 2010; 76: 753–765 © Georg Thieme Verlag KG and antifeedant [9] activities as well as activity duced the gastric secretions (3.9 ± 1.0 to 0.5 ± Stuttgart · New York · against Ehrlichʼs ascites tumor in mice [10]. An al- 0.2 mL/4 h), and total acid secretion (34.4 ± 11.0 ISSN 0032‑0943 coholic extract of the P. barbatus roots was shown to 2.7 ± 0.5 mEq/L) and raised gastric pH (2.2 ± 0.3 Correspondence to exhibit marked inhibitory action against Esche- to 6.5 ± 0.8) in rats. The treatment with WE (2 g/ Prof. Dr. Matthias F. Melzig richia coli toxin-induced secretory response in kg p.o.) was also found to protect against lesions Institute of Pharmacy rabbits and guinea pig ileal loops [11]. It has been induced by ethanol or cold-restraint stress, in py- Free University Berlin Königin-Luise-Str. 2 + 4 shown that a hydroalcoholic extract of P. barbatus lorus-ligated rats [14]. Similar results were ob- 14195 Berlin (880 mg/kg/day) exerted a variety of toxic effects tained by Schultz et al. [15] who reported that Germany on the different periods of pregnancy in rats; for the WE of the leaves (0.5–0.1 g/kg) injected into Phone: + 493083851451 Fax:+493083851461 example, in the period before embryo implanta- the duodenal lumen decreased the volume (62 [email protected] tion, it caused a delay in fetal development and and 76%) and total acidity (23 and 50%) of gastric Alasbahi RH, Melzig MF. Plectranthus barbatus: A Review… Planta Med 2010; 76: 753–765 754 Reviews acid secretion in pylorus-ligated mice. The water extract of P. bar- Pharmacological effects of forskolin batus leaves administered by gavage to young rats with and with- cAMP-dependent effects: A number of studies on the various out cholestasis was reported to reduce weight gain, feed inges- pharmacological effects of forskolin have been conducted mainly tion, and energy utilization in both groups in the same propor- on laboratory animals but a few on humans. The fact that forsko- tion. However, the water extract was found to inhibit, partially, lin directly activates adenylyl cyclase and thus increases cAMP the increase in liver wet weight, liver fat content and the serum levels is considered as the mechanism of action that underlies levels of cholesterol and triacylgycerides caused by cholestasis the various pharmacological effects of forskolin. The following is [16]. Furthermore, P. barbatus extract fed to ovariectomized rats a summary of the main pharmacological effects of forskolin was found to reduce body weight, food intake and fat accumula- mediated by the increase of the cAMP. tion [17]. The essential oil extracted from the leaves of P. barbatus Cardiovascular effects: Forskolin was found to exert positive ino- and one of its major components, i.e., α-pinene, were reported to tropic actions on the isolated guinea pig heart, isolated rabbit have a direct relaxant and spasmolytic effect on the guinea pig heart and on the dog and cat heart in situ. In addition, forskolin ileum [13]. augmented coronary blood flow in the isolated guinea pig heart. A variety of pharmacological activities of P. barbatus were the It was reported that forskolin increased the heart rate and low- subjects of a number of patents, for example, antispasmodic ef- ered the blood pressure in dogs, cats, rats and rabbits and also in fects on smooth muscle of the respiratory system, antiasthmatic, spontaneously hypertensive and renal hypertensive rats. The car- cough-relieving and phlegm-expelling [18–20], inhibition of the diovascular effects of forskolin such as the inotropic effect could absorption of alveolar bones [21], reduction of the total body be explained primarily by the increase of cAMP in heart muscle, weight [22,23], induction of lipolysis in rat adipose tissue [24] which is known to increase its contractility via opening of the and inhibition of the α-glucosidase [25] as well as promotion of slow Ca2+-channels, thus leading to elevation of intracellular cal- subcutaneous fat decomposition [26]. Other patents presented cium, and the hypotensive effect by the increase of cAMP in the an antiallergic effect [27], hair-loss preventing effect, and activa- vascular smooth muscle, which causes a relaxation due to the tion of the process of melanogenesis [28], an antiaging effect [29] lowering of the calcium sensitivity of the contractile system of as well as antimicrobial activity of the essential oil, with a certain smooth muscle cells [5,48–50]. However, the inotropic and chro- composition (at least 7.5% bornyl acetate, 3.5% 3-decanone, notropic effects of forskolin in conscious dogs were reported to 3.75% of an azulene derivative, 1% α-pinene, and 0.75% β- be not only due to direct activation of adenylyl cyclase, but also pinene), extracted from P. barbatus root [30]. mediated by neural mechanisms and potentiated by the prevail- Adverse effects of Plectranthus barbatus: P. barbatus was reported ing level of sympathetic tone [51]. to cause perianal dermatitis [31]. It has been demonstrated that forskolin exhibited concentration- dependent inhibitory effects on vascular contractility of rat aorta Forskolin by decreasing the cytosolic Ca2+ level at a lower concentration Forskolin (26) (see Fig. 2 in Part 1 of our Review [DOI: 10.1055/s- (0.1 µM) and decreasing the sensitivity of contractile elements 0029-1240898]) is one of the most extensive studied constitu- to Ca2+ at a higher concentration (1.0 µM) [52]. Repolarization ents of P. barbatus. A great number of studies revealed the unique and reduction in the intracellular Ca2+ sensitivity of force was character of forskolin as a direct, rapid and reversible activator of found to be the primary mechanism of forskolin-induced relaxa- adenylyl cyclase, which results in marked increases in the level of tion of intact rat tail artery [53]. Forskolin as a vasodilator was re- intracellular cyclic 3′,5′-adenosine monophosphate (cAMP) in a ported to open the large-conductance calcium-activated potassi- variety of mammalian membranes, broken cell preparations and um channels in coronary myocytes by cross-activation of protein intact tissues [32–42]. Forskolin in the form of forskolin affinity kinase C. This signaling pathway represents a novel mechanism columns has thus been used for the purification of the enzyme for regulation of potassium channel activity in various smooth adenylyl cyclase [43,44]. Adenylyl cyclase exists in at least nine muscle and other cells [54]. In addition, forskolin-induced relax- different membrane-associated isoforms and each isoform shows ations of isolated rabbit aortic preparations, accompanied by in- distinct patterns of tissue distribution and biochemical/pharma- creased cAMP were found to interact with endothelium-derived cological properties.

Load more