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COLEUS FORSKHOLII: PHYTOCHEMICAL AND PHARMACOLOGICAL PROFILE

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COLEUS FORSKHOLII: PHYTOCHEMICAL AND PHARMACOLOGICAL PROFILE

Mridul Bhowal *and Darshika M. Mehta

PES College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bengaluru - 560050, Karnataka, India.

ABSTRACT: Coleus forskohlii is an herb historically used in Ayurvedic medicine. Nowadays Coleus forskohlii is used as a fat burning supplement in various formulations and available in the Indian market. Forskolin the main constituent of this plant is used to treat allergies, skin conditions such as eczema and psoriasis, painful menstrual periods, irritable bowel syndrome (IBS), urinary tract infection (UTI), bladder infections, advanced cancer, blood clots, sexual problem in men, insomnia, and convulsions. Healthcare providers sometimes give forskolin intravenously (by IV) for heart failure. Some people breathe in (inhale) forskolin powder for asthma. Forskolin drops are used in the eyes to treat glaucoma. Because of its wide use, this plant some time been adulterated with its species and other varieties. The standardisation parameters are important for this plant in every herbal formulation. With the developments in modern instrumental methods it is high time for the herbal drug manufacturers to come out with the standard level of this drug to be included in the formulation. An extensive study of phytochemical constituents reported from Coleus forskohlii and pharmacological activities carried out are enlisted in this article.

Keywords:

Coleus forskohlii, Forskolin, Phytochemical, Pharmacological, obesity, Volatile oil, Anti-diabetic

INTRODUCTION: Medicinal plants are known as sources of phytochemicals, which are widely sought after worldwide for their natural properties. They are of great significance to the health of individuals and communities 1. In many countries, herbal remedies are making a comeback as an alternative to modern medicine. India is one of the twelve mega biodiversity hot spot regions of the world and one fifth of all plants found in India are used for medicinal purpose 2. Coeleus forskholii Briq. [Syn. Coeleus barbatus (Andr.) Benth] belonging to the family Lamiaceae is indigenous to India 3.

The Indian herbal industries recognize it as most medicinally and economically important. Tuberous roots of coleus are found to be a rich source of Forskolin (Coleonol) 4.  Forskolin has a unique property of activating almost all hormone sensitive adenylate cyclase enzymes in a biological system 5. It’s used as a potential drug for hypertension, congestive cardiac failure, respiratory disorders, eczema, painful urination, colic, convulsions and insomnia 6.  Forskolin is reported to be useful in the treatment of glaucoma, asthma and certain type of cancers 7. In addition, it has been shown to have anti-inflammatory property 8.

The genus Coleus was first described by De Loureiro in the year 1970. The name Coleus is derived from the Greek word Koleos, which means sheath around the style 9. The species name forskohlii was given to commemorate the Finnish botanist, Forskel. More than 150 species belong to genus Coleus.

In India, the major medicinal species of Coleus is the tuberous C. forskohlii; C. amboinicus, C. blumei, C. zeylanicus, C. malabaricus and C. scutellaroides and other species are mainly used to treat dysentery and digestive disorders 10, 11. C. forskohlii, apart from its medicinal use is also used as a potent source of essential oil 12. The essential oil present in tubers has an attractive and delicate odour with a spicy note 13. The essential oil has potential use in the food flavouring industry and can be used as an antimicrobial agent 14.

The focus of this review is to provide information on the advancement in the ethnopharmacological, phytochemical, pharmacological and toxicological profile of Coleus forskohlii.

Plant Profile: Coleus forskohlii is indigenous to India 3 and is recorded in Ayurvedic Materia Medica under the Sanskrit name ‘Makandi’ and ‘Mayani’12, 15.

Taxonomical Hierarchy: 16, 17

Kingdom:    Plantae

Divison:      Magnolophyta

Class:          Magnoliopsida

Order:          Lamiales

Family:        Lamiaceae

Genus:          Coleus

Species:        Forskohlii

Vernacular names:

Sanskrit 12, 15:    Makandi, Pashanbhed, Mayani

Kannada:           Makandiberu

English:             Coleus

Hindi:                Patharchur

Bengali:             Paterchur

Geographical Distribution: Coleus forskohlii is an aromatic herbaceous species of medicinal importance. Indian sub- continent is considered as the place of origin of C. forskohlii 4, 12. It grows wild in the sub-tropical warm temperate climates of India, Nepal, Burma, Sri Lanka and Thailand. Apparently, it has been distributed to Egypt, Arabia, Ethiopia, tropical East Africa and Brazil11, 18, 19. In India, the crop is cultivated in the parts of Gujarat, Maharashtra, Rajasthan, Karnataka and Tamil Nadu. In Tamil Nadu, it is approximately grown in Salem, Dharmapuri, Trichy, Erode, Coimbatore and Dindigul districts of 6000 acres. It grows wild in the Himalayan region from the Shimla hills extending throughout the Kumaon and Garhrwal hills, Parasnath hills of Bihar and Western Ghats 19.

Botanical Description:

TABLE 1: BOTANICAL FEATURES OF COLEUS FORSKOHLII

Plant

“Coleus forskohlii”

 Overall Height:

45-60cm
Leaves Size Length: 7.5-12.5cm
Width: 3-5cm
Shape Tear drop shape
Colour Shimmering green framing bright purple centre; varies depending on the amount of shade.
Features Pubescent, narrowed into petioles
Inflroscence Raceme; length: 15-30cm
Flowers Stout; size ranges from 2-2.5cm;

perfect and calyx inside
Calyx Upper lip of calyx is broadly ovate
Ovary Ovary is four parted and stigma is two lobed.
Root Colour Golden brown
Type Fibrous, thick, radially spreading, tuberous and fasciculated
Shape Conical fusiform
Size Length: 20cm
Diameter: 0.5-2.5cm
Odour Strongly aromatic

FIG. 1 FIG. 2 FIG. 3 FIG. 4

FIG. 1: (A, D) COLEUS FORSKOHLII PLANT, (B) COLEUS FORSKOHLII TWIG, (C) ROOTS

Ethnnopharmacology: Traditionally, the roots have been used as condiments in pickles and also for medicinal purposes by the ayurvedic schools of medicines 20. Root juice is given to children suffering from constipation 21. Kothas, the native tribes of Trichigadi (Kota) in Nilgiri, South India consider the decoction of tuberous roots as tonic 22. Ethnomedicinal uses of Coleus forskohlii for relief of cough, eczema, skin infections, tumors and boils were also reported 23. In Ayurvedic system of medicine, Coleus forskohlii has been used to treat hypertension, congestive heart failure, eczema, colic, respiratory disorders, painful urination, insomnia, and convulsions, asthma, bronchitis, intestinal disorders, burning sensation, constipation, epilepsy and angina 20.Clinical studies of the plant and the forskolin constituent support these traditional uses, but also indicate that it may have therapeutic benefit in psoriasis, and prevention of cancer metastases 8.

Phytochemistry: The major constituent which has been reported from Coleus forskohlii are diterpenoids and essential oils. The tuberous root extracts of C. forskohlii contain minor diterpenoids i.e., deactylforskolin, 9-deoxyforskolin, 1, 9-deoxyforskolin, 1, 9-dideoxy-7-deacetylforskolin in addition to forskolin (7 β- acetoxy - 8, 13-epoxy-1α, 6 β, 9 α - trihydroxylabd-14-en-11-one) which is the principle bioactive constituent of Coleus forskohlii 10, 24. 1,6-diacetoxy-9-deoxyforskolin, forskolin I, forskolin J, and forskolin L was isolated and reported from the Chinese species 25.  Two more diterpenoids i.e., 6-acetyl-1-deoxyforskolin and 6-acetyl-1,9-dideoxy forskolin were also reported 26.  Further studies reports the presence of various forskolin derivatives  like forskolin E, forskolin F or coleonol D,  forskolin G, and  forskolin H 27. Jin and He 28 in the year 1998 isolated and reported 1-acetyl forskolin, Isoforskolin or coleonol B, and 1,6-di-O-acetylforskolin.

In the year 2007, Shan et al., 29, extracted two diterpene glycosides namely forskoditerpenoside A and forskoditerpenoside B from the ethanol extract of the whole plant of Coleus forskohlii. Later, three new minor labdane diterpene glycosides, forskoditerpenoside C, forskoditerpenoside D, forskoditerpenoside E and a nobel labdane diterpene forskoditerpene A were isolated from the ethanolic extract of the whole plant of Coleus forskholii 30. Coleonol E and Coleonol F are reported from Indian species 31.

Coleol and coleosol were isolated from the roots of C. forskohlii 32. In the Kenyan species coleon O and plectrin were reported from their leaves 33. A study on whole plant extract conducted by Shan and Kong 34 in the year 2006, reports the presence of 3-hydroxy forskolin and 3-hydroxyisoforskolin.

TABLE 2: THE DITERPENOIDS ISOLATED FROM COLEUS FORSKOHLII ALONG WITH THEIR STRUCTURES AND PLANT PARTS USED

S.no. Name of the compound Structure Plant parts used Ref.
                                       Abietane diterpenoids
1. Abietatriene

(dehydroabietane)

 

  FIG. 1 Roots

 

 35
2. 7β-Acetyl-12-deacetoxycyclobutatusin

 

 

     FIG. 2 Leaf 36
3. (+)-Allylroyleanone (plectranthone J)

 

    FIG. 3 Leaf 37
4. Barbatusin

 

  FIG. 4 Leaf 36, 38, 39
5. Barbatusol FIG. 5 Stem 40
6. Coleon C  FIG. 6 Whole Plant 41
7. (16R)-Coleon E  FIG. 7 Leaf 37, 42
8. Cariocal  FIG. 8 Stem 43
9. Coleon F  FIG. 9 Leaf 37, 44
10. Coleon O  FIG. 10 Leaf 33
11. Coleon S  FIG. 11 Leaf 45, 46
12. Coleon T  FIG. 12 Leaf 45, 46
13. Cyclobutatusin

 

 FIG. 13 Leaf 36, 38, 47
14. Demethylcryptojaponol (11-hydroxysugiol)

 

 FIG. 14 Roots 48
15. 20-Deoxocarnosol

 

  FIG. 15 Stem 49, 50
16. 14-Deoxycoleon U

 

  FIG. 16 Roots 48
17. Ferruginol

 

  FIG. 17 Stem 40
18. 3β-Hydroxy-3-deoxybarbatusin

 

  FIG. 18 Leaf 38
19. Plectrin

 

  FIG. 19 Leaf 33, 37
20. (16R)-Plectrinon A

 

  FIG. 20 Leaf 37, 51
21. Plectrinon B

 

  FIG. 1 Leaf 37
22. Sugiol

 

  FIG. 2 Whole Plant 52
                8,13-Epoxy-labd-14-en-11-one-diterpenoids
23. 1-Acetoxy coleosol

 

 FIG. 3 Roots 53
24. 6-Acetyl-1-deoxyforskolin

 

 

  FIG. 4 Whole Plant 26
25. 1-Acetylforskolin

 

  FIG. 5 Roots, Whole Plant 28, 54, 55
26. 6-Acetyl-1,9-dideoxyforskolin

 

  FIG. 6 Whole Plant 26
27. Coleol

 

  FIG. 7 Roots 32,56,

57, 58
28. Coleonol E

 

  FIG. 8 Roots 59
29. Coleonol F

 

  FIG. 9 Roots 59
30. Coleosol

 

  FIG. 10 Roots 32, 60
31. 7-Deacetylforskolin

 

  FIG. 11 Roots 28, 54, 55,

56, 61, 62
32. Deacetyl-1-deoxyforskolin

 

  FIG. 12 Roots 56
33. Deoxycoleonol

 

  FIG. 13 Roots 63
34. 9-Deoxyforskolin

 

  FIG. 14 Roots 56, 61, 64
35. 1,6-Diacetoxy-9-deoxyforskolin

 

  FIG. 15 Roots, Whole Plant 26, 52, 65
36. 1,9-Dideoxy-7-deacetylforskolin

 

  FIG. 16 Roots 56, 61, 62
37. 1,9-Dideoxyfoskolin  FIG. 17 Roots 56, 61, 62
38. 1,9-Dideoxycoleonol B

 

  FIG. 18 Roots 53
39. Forskolin

 

 FIG. 19 Roots 3, 56, 61,

62, 66, 67
40. Forskolin E

 

  FIG. 20 Roots, Whole Plant 28, 68
41. Forskolin F

 

  FIG. 1 Roots, Whole Plant 27, 28,

32, 56,  68
42. Forskolin G

 

  FIG. 2 Roots, Whole Plant 25, 27,

69, 70, 71
43. Forskolin H

 

  FIG. 3 Roots, Whole Plant 25, 27,

71, 72
44. Forskolin I

 

  FIG. 4 Roots, Whole Plant 25, 65,

69, 72
45. Forskolin J

 

  FIG. 5 Roots 25, 65, 72
46. 6β-Hydroxy-8,13-epoxy-labd-14-en-11-one

 

  FIG. 6 Roots 25,

57, 65
47. Isoforskolin

 

  FIG. 7 Roots 25, 28, 32, 45, 54, 55, 62, 67, 69, 73
48. 11-Oxomanoyloxide

 

  FIG. 8 Roots 56
           8,13-Epoxy-labd-diterpenoids with some deviations
49. Coleonol

 

 FIG. 9 Roots 63
50. Coleonone

 

  FIG. 10 Roots 57, 58
51. 13-Epi-9-deoxycoleonol

 

  FIG. 11 Roots 74
52. 3-Hydroxyforskolin

 

  FIG. 12 Whole Plant 34
53. 3-Hydroxyisoforskolin

 

  FIG. 13 Whole Plant 34
54. Manoyl oxide

 

 FIG. 14 Roots 35
55. Coleolic acid

 

  FIG. 15 Whole Plant 75
56. Coleonic acid

 

  FIG. 16 Whole Plant 75
57. Forskoditerpene A

 

  FIG. 17 Whole Plant 30
58. 13-Epi-sclareol

 

  FIG. 18 Roots 76
                 8,13-Epoxy-labd-14-en-11-one-diterpene glycosides
59. Forskoditerpenoside A

 

  FIG. 19 Whole Plant 29
60. Forskoditerpenoside B FIG. 20 Whole Plant 29
61. Forskoditerpenoside C

 

  FIG. 21 Whole Plant 30
62. Forskoditerpenoside D

 

  FIG. 22 Whole Plant 30
63. Forskoditerpenoside E  FIG. 23 Whole Plant 30

Pharmacological Profile: Coleus forskohlii has been used as a potential drug for hypertension, congestive cardiac failure, respiratory disorders, painful urination, colic, convulsions and insomnia 6. It has been shown to have anti-inflammatory property as well 8. Clinical studies of the plant and the forskolin constituent support these traditional uses but also indicate that it may have therapeutic benefit in asthma, angina, psoriasis, and prevention of cancer metastases. The pharmacological studies carried out so far on Coleus forskohlii are given in Table 3.

TABLE 3:  PHARMACOLOGICAL ACTIVITIES REPORTED FROM COLEUS FORSKOHLII

S. no. Activity Action References
1 Antiglaucoma/Reduction in Intra Ocular Pressure (IOP) Forskolin suspension (1% forskolin) obtained from

Coleus forskholii lowers the IOP in rabbits, monkeys,

and humans by reducing the net aqueous inflow.

 77
2 Asthma Forskolin the active constituent of Coleus forskholii was

studied as bronchodilator for its potential use in asthma.

It blocked bronchospasm and bronchitis in guinea pigs

caused by histamine and leukotriene C-4

 78
3 Antiobesity The antiobesity effects of were investigated in ovariectomized

rats and the administration of Coleus forskholii extracts reduced

body weight, food intake and fat accumulation in those rats.

 79
4 Antiplatelet The antiobesity effects of were investigated in ovariectomized rats

and the administration of Coleus forskholii extracts reduced body weight, food intake and fat accumulation in those rats

 80
5 Antimicrobial A study on antimicrobial efficacy of Coleus forskholii against Staphylococcus aureus shown both bacteriostatic and bacteriocidal activity at Minimum Inhibitory Concentration (MIC) values ranging from 60 to 300μg/ml. 81
6 Anti-inflammatory Forskolin administered through i.p. route significantly inhibits Carrageenan-induced paw edema in a dose-dependent manner in rats. Similar effects were also observed in adjuvant induced polyarthritis and Croton oil-induced ear inflammation in rats 8
7 Antihypertensive Studies shown that forskolin increases the heart rate, and lowers the blood pressure in dogs and cats and also in spontaneously hypertensive and renal hypertensive rats.

Another study reports that coleonol (distereoisomer of forskolin)

isolated from a 50% ethanol extract of Coleus forskholii have

lowered the blood pressure of anesthetized cats and rats, as well

as spontaneously hypertensive rats, due to the relaxation of the

vascular smooth muscle.

 20, 82
8 Antimetasatic & Antiproliferative Forskolin was proved as a potent inhibitor of cancer metastasis in mice injected with malignant cells. As little as 82mcg administered to mice inhibited metastatsis by 70%. 13-epi-sclareol showed antiproliferative activity in breast and uterine cancer cells in vitro. Coleon C when investigated on eight human tumor cell lines for its antiproliferative activity it was observed that the A375 was the most sensitive of all the cell lines and it was concluded that coleon C could effectively  inhibit tumour cell proliferation and growth by inducing apoptosis with low toxicity. Barbatusin is reported to inhibit Lewis lung carcinoma and lymphocytic leukemia P 388 in mice 38, 77, 83, 84
9 Antidepressant Forskolin indicates a strong antidepressant when studied using the forced swimming method in rats. Forskolin (0.01-0.1 mg/kg) dose-dependently decreased ratings of immobility, with effects similar to those of amitriptyline treatment.  The maximum effects of forskolin were observed at 0.01 mg/kg dose which is 150 more times potent than that (15 mg/kg) of amitriptyline 85
10 Antidyspeptic The aqueous extract of Coleus forskholii decreases gastric secretion indicating antidyspeptic activity, and protects against stress induced gastric ulcers. 86
11 Antioxidant Studies were carried out for the antioxidant properties of Coleus forskholii and it was observed that the tubers possessed significant potential of both enzymatic and non-enzymatic antioxidants that could protect against oxidant and free radical injuries, in addition to having their medicinal properties 87
12 Antiulcer Studies shows that Plectrinon A inhibites the gastric H+, K+-ATPase, more effectively than the classic proton pump inhibitor omeprazole. This may be the mechanism underlying the anti-ulcer property of Coleus forskohlii 52
13 Antidiabetic Forskolin stimulates glucose-induced insulin secretion in vitro. This appears to reflect a general stimulatory influence of forskolin on adenylate cyclase activity, obviating its specific suitability as an antidiabetic treatment 88, 89
14 Antimycotic Antifungal studies were carried out on different fungi like Aspergillus flavus, Trichoderma rubrum, and Microsporum gypseum and it was observed that chloroform extract shows maximum inhibitory activity 90
15 Hepatoprotective Forskolin and 1,9-dideoxyforskolin are efficacious agonist of the pregnane X receptor (PXR, NR1I2) and thus there is activation of  PXR which mediates the hepatoprotective effect 91
16 Hypothyroidism Forskolin and 1,9-dideoxyforskolin are efficacious agonist of the pregnane X receptor (PXR, NR1I2) and thus there is activation of  PXR which mediates the hepatoprotective effect 92
17 Immune System Enhancement Forskolin exhibits potent immune system enhancement (primarily through activation of macrophages and lymphocytes) in several models. 93, 94, 95
18

 

 Psoriasis Clinical studies were conducted in four patients with psoriasis and it was observed when they were given forskolin, there were improvement in psoriatic symptoms. The ability of forskolin to regulate cAMP levels in skin cells has been shown to have therapeutic benefit for sufferers of psoriasis 21
19 Relaxative effects forskoditerpenosides A and B isolated from the ethanol extract of the whole plant of Coleus forskholii showed relaxative effects on isolated guinea pig tracheal spirals in vitro. 29
20 Urinary Tract Infection (UTI Forskolin when injected directly into the bladder or administered intravenously to type 1 fimbriated uropathogenic Escherichia coli infected mice, it induced exocytosis of bladder epithelial cells fusiform vesicles in which E. coli is incorporated and thus reduced the number of intracellular E. coli and exposed the bacteria to the antibiotics 96
21 Vasculogenic properties Investigations on forskolin for vasculogenic impotence were carried out and it was observed that forskolin can be used as an addition to a standard 3-agent pharmacotherapy for erectile dysfunction. Other in vivo and in vitro studies were carried out which elicits a possible role of forskolin in treating this condition. 97, 98

Toxicology: Coleus forskohlii and forskolin extracts have an excellent safety profile and are generally non-toxic or have no side effects at the recommended dosage 99. Sclareol isolated from C. forskohlii reported to be non–cytotoxic to resting human peripheral blood mononuclear leukocytes and have LD50 > 5mg/kg in rat 100. The study on forskolin showed that it was extremely safe with an oral LD50 of 3100 mg/kg 101. Hydroalcoholic extract of Coleus forskohlii has been shown to interfere with embryonic implantation and to delay fetal development 102.

CONCLUSION: India is the leading exporter of Coleus forskohlii extracts and its products to several countries. The main users of Coleus are United States, Poland, South Korea, Australia, Japan, Italy, Spain, South Africa and Canada.  Indian herbal industries has to utilise the opportunity by providing the quality formulations by standardising the product with respect to the marker compounds. There is an enormous opportunities to market Coleus forskohlii and its formulations in other countries too. Department of Ayush and other Government governing bodies have to encourage the herbal drug manufacturers to set up the quality control parameters.

ACKNOWLEDGEMENT: The authors are highly thankful to Prof. Dr. J. Saravanan, Principal, PES College of Pharmacy for the needful support.

CONFLICT OF INTEREST: The authors declared no competing interests.

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    How to cite this article:

    Bhowal M and Mehta DM: Coleus forskholii: Phytochemical and Pharmacological profile. Int J Pharm Sci Res 2017; 8(9): 3599-18.doi: 10.13040/IJPSR.0975-8232.8(9).3599-18.

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IJPSR

M. Bhowal *and D. M. Mehta

PES College of Pharmacy, Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India.

mridul.bhowal@gmail.com

13 February, 2017

25 July, 2017

12 August, 2017

10.13040/IJPSR.0975-8232.8(9).3599-18

01 September, 2017

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