CHAPTER 28

Antidiabetic andAntihyperlipidemicActivity of Bonducella(Caesalpinia bonducella)Seeds

Dayanand M. KannurDepartment of Pharmacognosy, Shree Chanakya Education Society’s, Indira College ofPharmacy, Pune, India

237

N

C

CHAPTER OUTLINE

Introduction 238Botanical Description 238Historical Cultivation and Usage 239Present-Day Cultivation and Usage 239

Pharmacognostical analysis 239

Extraction process of the bonducella

seed 240

Applications to Health Promotion andDisease Prevention 241

uts & Seeds in Health and Disease Prevention. DOI: 10.1016/B978-0-12-3756

opyright � 2011 Elsevier Inc. All rights reserved.

Antidiabetic potential of Caesalpinia

bonducella seeds 241

Antihyperlipidemic activity of Caesalpinia

bonducella seeds in hyperglycemic

conditions 241

Adverse Effects and Reactions (Allergiesand Toxicity) 243Summary Points 244References 244

LIST OF ABBREVIATIONS

BGL, blood glucose level

BUN, blood urea nitrogen

HDL, high density lipoprotein

KEE, seed kernel ethanolic extract

LDL, low density lipoprotein

LD50, lethal dose

PEE, seed kernel petroleum ether extract

SC, serum creatinine

SEE, ethanolic extracts of the seed coat

TC, total cholesterol

88-6.10028-3

FIGURE 28.1Caesalpinia bonducella. (A) pla

238

PART 2Effects of Specific Nuts and Seeds

INTRODUCTIONCaesalpinia bonducella (synonym Caesalpinia bonduc) is a plant belonging to the Caesalpi-

niaceae family. It is one of the important herbs found in folklore medicine, and itsmedicinal uses have been quoted in various Ayurvedic texts and scriptures. Traditionally, it is

used to cleanse the uterus in the postpartum period, and also acts as a uterine stimulant. It is

known to alleviate fever, edema, and abdominal pain during this period. Caesalpiniabonducella is a prickly shrub and has numerous synonyms, including Duhsparsa (“difficult

to touch”), Kantaki karanja (“having prickles”), Vajra bijaka (“having hard seeds”); Kanta

phala (“fruits covered with prickles”), etc. It has many other common names, includingfever nut, Indian filbert, and nickar (English); Karanja, Kanthekaranja, Karanjuvu, Karanju,

and Lata Karanju (Hindi); Gajaga, Sagargota, Kanchaki, and Karbath (Marathi); and Akit-

makit and Bunduk (Urdu).

BOTANICAL DESCRIPTIONCaesalpinia bonducella is a large, straggling, very thorny shrub, and is an extensive climber. Thebranches are armed with hooks and are straight, hard yellow prickles (Kirtikar & Basu, 1995).

nt; (B) Inflorescence; (C) Pod; (D) Seeds; (E) Kernels; (F) Pods and seeds.

CHAPTER 28Bonducella Seeds and Antidiabetic Activity

239

The leaves (see Figure 28.1A) are compound, 30e60 cm long, with prickly petioles. Thestipules have a pair of round pinnae at the base of the leaf, each furnished with a long

mucronate point. There are six to eight pairs of pinnae, 5e7.5 cm long, with a pair of

hooked stipulary spines at the base, and six to nine pairs of leaflets, 2e3.8�1.3e2.2.Leaflets are membranous, ellipticeoblong, obtuse, strongly mucronate, glabrous on the

upper surface and more or less puberlous beneath; the petilolules are very short(Sutaria, 1969).

The flowers are pale yellow in color, dense (usually spicate), with a long peduncled terminal

and supra-axillary racemes at the top. Racemes droop downwards and are 15e25 cm long; thepedicles are very short in bud, elongating to 5mm in flowers and 8mm in fruit; they are

brown, downy and oblanceolate. Filaments are declinate, flattened at the base, and clothed

with long white silky hairs (Figure 28.1B). The flowering season starts in June, and the shrubbears fruits by November.

The fruits are inflated oblongate pods, 5e7.5� 4.5 cm, covered with prickles, containingone or two seeds per pod. The pods have short stalks. The seeds are 1e2 cm in size, globular,

hard, bluish-gray in color, and have a smooth, shiny surface (Sutaria, 1969)

(Figure 28.1CeF).

HISTORICAL CULTIVATION AND USAGECaesalpinia bonducella is a large, prickly shrub that grows naturally throughout the hotter partsof India, Myanmar, Sri Lanka, and the West Indies, along the sea coasts and at heights of up to

800 meters on the hills. It is commonly found in the southern part of India.

Caesalpinia bonducella seeds have long been used in traditional medicine in treating

symptoms and ailments, including abdominal pain, colic, leprosy, fever, edema, and

malaria. It is also used as a uterine stimulant, and to cleanse the uterus during the post-partum period.

PRESENT-DAY CULTIVATION AND USAGECaesalpinia bonducella is propagated by seeds. These are sown at the start of the rainy season;

they are first soaked overnight, and then generally sown at intervals of 50 cm to forma hedge. It is essential to irrigate immediately after sowing the seeds. Sandy loam soil

gives optimum growth. After 3e4 weeks the plants sprout, growing to their maximum

height in 2 to 2½ years. In the initial stages it is very important to irrigate, and plantsshould be pruned every fortnight.

Pharmacognostical analysis

Caesalpinia bonducella seed kernels (Figure 28.1E) are oblong to ovoid in shape, brittle, pale

yellow to cream in color, with a characteristic odor and bitter taste. The seed coat is brownish-gray in colour, with a characterisic odor and an astringent taste (Figure 28.1D).

The seeds contain furanoditerpenes (Peter et al., 1997) a-caesalpin, b-caesalpin, g-caesalpin,d-caesalpin, e-caesalpin, and caesalpinia-F (Keitho et al., 1986); fatty acids (palmitic, stearic,

octadeca-4-enoic and octadeco-2-4-dienoic, lignocenic, oleic and linoleic); phytosterinin;

b-sitosterol; a homoisoflavone, bonducellin (Purushothaman et al., 1982); amino acids(aspartic, arginine, and citrulline); carbohydrates (starch, sucrose); b-carotene; a glycoside,

bonducin; and gums and resins (Williamson, 2002).

Caesalpinia bonducella fruits contain D(þ) pinitol, and the leaves contain the glycosidalcompounds Brazilin and bonducin. The roots contain cassane furan diterpene caesalpinin;

cassane diterpenes caesaldekarins C, F, and G; bonducellpins A, B, C, D (Peter & Tinto, 1997);

and the steroidal saponin diosgenin (Figure 28.2).

FIGURE 28.2Chemical constituents of Caesalpinia

bonducella.

PART 2Effects of Specific Nuts and Seeds

240

Extraction process of the bonducella seed

Extraction is carried out by breaking the seed coat; the kernels are then crushed to a coarsepowder. This powder is defatted with petroleum ether (60/80). The petroleum ether is distilled

off on a rotary flash evaporator to leave a yellow, oily extract (22% w/w). The defatted marc is

then dried and further extracted with 95% ethanol, which yields a sticky ethanolic reddishbrown extract (16% w/w).

The physical constants of Caesalpinia bonducella are shown in Table 28.1; results of the analysisof the fixed oil obtained from the seed kernels are shown in Table 28.2.

TABLE 28.1 Determination of Physical Constants of Caesalpinia bonducella Seeds

SL No. Quantitative Standards Seed Kernels (% w/w) Seed Coat (% w/w)

1 Loss on drying 10.22 10.062 Extractives:

a) Water solubleb) Alcohol solublec) Pet. ether

52.0021.4444.80

36.2014.6403.36

3 Ash values:a) Total ashb) Acid-insoluble ashc) Water-soluble ash

2.601.560.87

3.401.941.07

TABLE 28.2 Analytical Values of Oil of Caesalpiniabonducella Seeds

Acid value 4.71Saponification value 144.46Ester value 139.75

CHAPTER 28Bonducella Seeds and Antidiabetic Activity

241

APPLICATIONS TO HEALTH PROMOTION AND DISEASEPREVENTIONCaesalpinia bonducella seeds have been used to cure various diseases and disorders. The seeds

are used as antidiabetics, and various scientific studies have proved their claim to activity. Theyhave been proven to be anti-inflammatory, anthelminitic, and antimalarial, and are also

effective as stomachic and digestives. They are used as a liver tonic in the treatment of jaundice

and various liver disorders. The seeds are also considered to be an aphrodisiac, and a generaltonic helping in the rejuvenation of the body (Shrikantha Murthy, 2000a). The roasted

seed powder is used as an antileprotic, antiperiodic, antipyretic, etc. The topical application

of seed oil helps in rheumatic disorders and arthritis.

In Indian traditional medicine, Caesalpinia bonducella is used in a vast range of diseases. It is the

best cure for abdominal pain due to flatulence. The roasted seed powder relieves pain when

administered in an oily formulation. A mixture of roasted seed powder, asafoetida, ghee, anda small amount of salt eliminates abdominal pain during the postpartum period (Shrikantha

Murthy, 2000b). It is the best medication for malaria, where a combination of the roasted seedpowder with Piper longum (1:1) is given with honey, approximately 0.5 g, three times a day for

3e4 days.

Antidiabetic potential of Caesalpinia bonducella seeds

The antidiabetic potential of Caesalpinia bonducella seeds has been investigated since 1987 by

Simon and colleagues, who showed that the aqueous extract possesses antihyperglycemic

action (Simon et al., 1987). Rao and colleagues found that the powder of Caesalpinia bonducellaexhibited antidiabetic potential, and they attributed this property to reduced absorption from

the gut (Rao et al., 1994). Sharma and colleagues (1997) suggested that the aqueous and 50%

ethanolic extracts of the seeds exhibited significant antihyperglycemic as well as hypoglycemicaction. They proposed that the action may be similar to that of Glibenclamide and stimulate

the b cells, enhancing the secretion of insulin.

Chakrabarti and colleagues strongly claim that the extracts of seeds of Caesalpinia bonducella

significantly lower the serum glucose level in type 2 diabetes (Chakrabarti et al., 2003);

they also investigated the insulin secretion stimulating potential of Caesalpinia bonducellaseeds and concluded that the antihyperglycemic activity exhibited is due to insulin

secretagogue activity (Chakrabarti et al., 2005).

Kannur and colleagues stated that the seed kernel ethanolic extract (KEE) and seed kernelpetroleum ether extract (PEE) as well as the ethanolic extracts of the seed coat (SEE) of C.

bonducella exhibited a remarkable blood glucose lowering effect in the glucose tolerance test

(Figure 28.3). These extracts also significantly lower the elevated blood glucose level in alloxaninduced hyperglycemia (Table 28.3; Figure 28.4) (Kannur et al., 2006), as well as elevated blood

urea nitrogen (Figure 28.5). All these studies prove that the seeds possess a strong capacity to

reduce an elevated blood glucose level, and thus can be used in treating diabetes mellitus.

Antihyperlipidemic activity of Caesalpinia bonducella seeds inhyperglycemic conditions

In most of the studies to date, the seeds of Caesalpinia bonducella have shown significantantihyperlipidemic actions. The effect of the extracts on diabetes-induced hyperlipidemia has

also been studied. It has been observed that due to diabetes, there is an increase in the total

cholesterol level as well as the triglyceride level (Kannur et al., 2006). In the diabetic animals,the HDL was reduced and the LDL level was increased significantly. All extracts of Caesalpinia

bonducella showed a significant decrease in the total cholesterol level and the triglyceride level

(Table 28.4). In particular, the kernel ethanolic extract (KEE) exhibited significant action. Italso increased the HDL and was successful in suppressing the LDL level as compared to the

standard drug (Figure 28.6).

0

20

40

60

80

100

120

140

0 30 90 150

BG

L

Time(mins)

Glucose tolerance level

GL (glucose loaded)

KEE (Kernel ethanolic extract)

PEE (petrol extract)

SEE (seed coat extract)

FIGURE 28.3Effect of Caesalpinia bonducella seed extracts in the glucose tolerance test.

TABLE 28.3 Effect of C. bonducella Extracts on the Blood Glucose Level (BGL), Blood Urea Nitrogen (BUN),and Serum Creatinine (SC) Levels in Alloxan-induced Hyperglycemia in Ratsa

Samples(mg%)

Normal DiabetesInduced

DiabetesDRosiglitazone0.01mg/kg

DiabetesDKEE

DiabetesDPEE

DiabetesDSEE

BGL 83.0� 2.42 578.0� 74.95 87.0c� 2.27 324.5b� 47.97 329.0b� 23.84 196.0c� 40.86BUN 27.85� 1.08 39.20� 3.11 28.65b� 2.85 22.22c� 0.83 33.35NS� 0.76 28.55c� 2.33SC 0.5� 0.04 0.7� 0.5 0.63NS� 0.3 0.63NS� 0.03 0.65NS� 0.03 0.65NS� 0.03

aGiven by oral route at dose of 300mg/kg; values are mean� S.E.M.bP< 0.05 when compared with diabetic control;cP< 0.001 when compared with diabetic control.NSNot significant.

0

100

200

300

400

500

600

mg

/m

l

Groups

Blood glucose level

Normal

Control

Standard

KEE

PEE

SEE

FIGURE 28.4Effect of Caesalpinia bonducella seed extracts on elevated blood glucose levels in diabetic rats.

PART 2Effects of Specific Nuts and Seeds

242

TABLE 28.4 Effect of C. bonducella Extracts on Total Cholesterol (TC), Triglyceride (TG), HDL, LDL, and VLDLLevels in Ratsa

Test(mg%)

Normal Diabetes Induced Standard KEE PEE SEE

TC 137.25� 1.89 177.00� 4.02 145.75� 7.09b 134.00� 7.62c 142.50� 2.63c 140.25� 2.10c

TG 88.75� 1.81 107.75� 5.75 93.25� 9.99b 88.50� 1.09c 94.00� 6.01b 86.00� 8.90c

HDL 44.25� 2.78 33.75� 1.43 42.00� 1.47c 49.25� 1.25c 41.25� 5.21c 37.75� 0.63b

LDL 75.75� 1.11 127.25� 2.16 85.75� 8.20c 67.50� 7.53c 83.00� 6.22c 85.75� 1.80c

aGiven by oral route at dose of 300mg/kg; values are mean� S.E.M.bP< 0.05 when compared with diabetic control;cP< 0.001 when compared with diabetic control.

FIGURE 28.5Effect of Caesalpinia bonducella seed extracts on blood urea nitrogen levels in diabetic rats.

0

50

100

150

200

TC TG HDL LDL

Mg

%

Normal

Diabetes induced

Standard

KEE

PEE

SEE

FIGURE 28.6Antihyperlipidemic action of Caesalpinia bonducella seed extracts. TC, total cholesterol; TG, triglyceride level; HDL, highdensity lipoprotein; LDL, low density lipoprotein.

CHAPTER 28Bonducella Seeds and Antidiabetic Activity

243

The presence of various sterols, and especially b-sitosterol, in the seeds may be responsible for

their antihyperlipidemic action.

ADVERSE EFFECTS AND REACTIONS (ALLERGIES AND TOXICITY)No serious adverse effects have been reported for Caesalpinia bonducella medicines, but over-

dosing can lead to nausea and vomiting. The LD50 has been found to be 3000mg/kg bodyweight (Kannur et al., 2006).

PART 2Effects of Specific Nuts and Seeds

244

SUMMARY POINTSl Caesalpinia bonducella seeds are a rich source of fixed oil. The seed kernels as well as the oil

obtained from them show significant pharmacological actions. Seed oil can be used asa rubefacient as well as an anti-arthritic agent.

l Caesalpinia bonducella has been extensively investigated for various medicinal attributes; it

has been validated scientifically, and can be used to treat inflammation andhyperlipidemia, as well as hyperglycemia. It can also be used as a stomachic. It is a proven

immunomodulator (Shukla et al., 2009a) as well as an adaptogenic agent. The seeds have

also been proven to be antioxidant (Shukla et al., 2009b) in nature.l The various studies carried out to date support the claims of Caesalpinia bonducella seeds as

a promising herbal antidiabetic drug. The extracts of Caesalpinia bonducella seeds may

stimulate the secretion of insulin by the beta cells, and thus show a blood-glucose loweringaction.

l The properties possessed by Caesalpinia bonducella have significant commercial value and

use. It is essential that investigations are carried out in more depth in order to validate otherclaims as well as to find out the constituents responsible for its antidiabetic potential.

ReferencesChakrabarti, S., Biswas, T. K., Rokeya, B., Ali, L., Mosihuzzaman, M., Nahar, N., et al. (2003). Advanced studies on

the hypoglycemic effect of Caesalpinia bonducella F. in type 1 and 2 diabetes in Long Evans rats. Journal of

Ethnopharmacology, 84, 41e46.

Chakrabarti, S., Biswas, T. K., Seal, T., Rokeyac, B., Ali, L., Azad Khan, A. K., et al. (2005). Antidiabetic activity of

Caesalpinia bonducella F. in chronic type 2 diabetic model in Long-Evans rats and evaluation of insulin secre-

tagogue property of its fractions on isolated islets. Journal of Ethnopharmacology, 97, 117e122.

Kannur, D. M., Hukkeri, V. I., & Akki, K. S. (2006). Antidiabetic activity of Caesalpinia bonducella seed extracts in rats.

Fitoterapia, 77, 546e549.

Keitho, P., Burke, A., & Chan, W. R. (1986). Caesalpin-F, a new furanoditerpene from Caesalpinia bonducella. Journal

of Natural Products, 49, 913e915.

Kirtikar, K. R., & Basu, B. D. (1995). Indian Medicinal Plants, 2, 842e845.

Peter, S. R., & Tinto, W. F. (1997). Bonducellpins AeD, new Cassane furanoditerpene of Caesalpinia bonducella.

Journal of Natural Products, 60, 1219e1221.

Peter, S. R., Tinto, W. F., McLean, S., Reynolds, W. F., & Tay, L.-L. (1997). Caesalpinin, a rearranged cassane fura-

noditerpene of Caesalpinia bonducella. Tetrahedron Letters, 38, 5767e5770.

Purushothaman, K. K., Kalyani, K., & Subramanian, K. (1982). Structure of boducellin, a new homoisoflavone from

Caesalpinia bonducella. Indian Journal of Chemistry, 21, 383.

Rao, V. V., Dwivedi, S. K., & Swarup, D. (1994). Hypoglycemic effect of Caesalpinia bonducella in rabbits. Fitoterapia,

LXV 245e247.

Sharma, S. R., Dwivedi, S. K., & Swarup, D. (1997). Hypoglycemic, antihyperglycemic and hypolipidemic activitiesof Caesalpinia bonducella. Journal of Ethnopharmacology, 58, 39e44.

Shrikantha Murthy, K. R. (2000a). Bhavaprakasa of Bhavamisra,Vol. 1, p. 246; Vol. 2, p. 627. Varanasi, India:

Krishnadas Academy.

Shrikantha Murthy, K. R. (2000b). Vagabhata’s Ashtang Hridayam, Vol. 2, p. 386. Varanasi, India: Krishnadas

Academy.

Shukla, S., Mehta, A., John, J., Mehta, P., Vyas, S. P., & Shukla, S. (2009a). Immunomodulatory activities of the

ethanolic extract of Caesalpinia bonducella seeds. Journal of Ethnopharmacology, 125, 252e256.

Shukla, S., Mehta, A., John, J., Singh, S., Mehta, P., & Vyas, S. P. (2009b). Antioxidant activity and total phenolic

content of ethanolic extract of Caesalpinia bonducella seeds. Food and Chemical Toxicology, 47, 1848e1851.

Simon, O. R., Singh, N., Smith, K., & Smith, J. (1987). Effect of an aqueous extract of Nichol (Caesalpinia bounduc)in blood glucose concentration: evidence of an antidiabetic action presented. Journal Council for Scientific and

Industrial Research (Australia), 6, 25e32.

Sutaria, R. N. (1969). A textbook of systematic botany, Vol. IV. Ahmedabad, India: Khadayata Book Depot. 177e179.

Williamson, E. M. (2002). Major herbs of Ayurveda. Sahibabad Ghaziabad, India: The Dabur Research Foundation &

Dabur Ayurvet Ltd.