Medicinal & Aromatic Plants

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Review Article - (2015) Volume 4, Issue 5

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The Tribe Caesalpinieae (Fabaceae): An Updated Review on Pharmacological Aspects

El-Nashar HAS, Eldahshan O and Singab AN*
Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, Abassia, 11566, Egypt
*Corresponding Author: Singab AN, Department of Pharmacognosy, Faculty of Pharmacy, Ain Shams University, Abassia, 11566, Cairo, Egypt, Tel: 20224051120, Fax: 20224051107 Email: ,

Abstract

Caesalpinieae tribe is one of the largest archaic tribes of subfamily Caesalpinioideae, family Fabaceae. Caesalpinieae tribe includes 9 subtribes that have more than 47 genera, including several valuable medicinal plants. Extracts of different plants of Caesalpinieae tribe were reported to possess a wide range of pharmacological activities, including anti-oxidant, anti-bacterial, anti-inflammatory, cytotoxic, anti-diabetic, antifungal, hepatoprotective, gastroprotective, analgesic, anti-arthritic, anti-filarial, antimalarial, anthelmintic, amoebicidal, diuretic, anti-psoriatic, anti-estrogenic, anti-fertility, wound-healing, anxiolytic, cardioprotective, immunomodulatory, anti-HIV activities. Thus, Caesalpinieae tribe includes several plants with a potential for exploitation as a source for plant-based pharmaceutical products. The present review could form a sound basis for further investigation in the potential discovery of new natural bioactive compounds and provide preliminary information for future research.

Keywords: Caesalpinieae; Tribe; Caesalpinioideae; Medicinal plants; Review; Pharmacological activities

Abbreviations

DPPH: 2, 2-Diphenyl-1-Picrylhydrazyl ROS: Reactive Oxygen Species

ABTS: 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) NO: Nitric Oxide

AST: Aspartate Aminotransferase ALT: Alanine Aminotransferase

ALP: Alkaline Phosphatase

Introduction

Medicinal plants as potential source of therapeutic aids have attained a significant role internationally for both human and animals, not only in diseased conditions but also as a potential material for maintaining health. There is currently a renewed interest in traditional medicine and an increased demand for drugs from plant sources. The revival of interest in plants derived medicines is mainly due to the current widespread belief that “Green medicine” is safe and more depend alone than costly synthetic drugs, many of which have serious side effects [1].

Caesalpinieae is one of the largest archaic tribes of subfamily Caesalpinioideae that belong to family Fabaceae, the members of tribe Caesalpinieae have been divided into eight to nine informal generic groups as Table 1 the Gleditsia group (2 genera), the Acrocarpus group (monogeneric), the Sclerolobium group (3 genera), the Peltophorum group (16 genera), the Caesalpinia group (12 genera), the Poeppigia group (monogeneric), Pterogyne group (monogeneric) , Dimorphandra group (10 genera) and a ninth informal group, the monogeneric Orphanodendron group which was added recently [2,3]. Caesalpinieae tribe includes about 47 genera and 430-440 species [4]. Several species in this tribe are well-known tropical ornamentals such as Flamboyant (Delonix regia) and Barbados Pride (Caesalpinia pulcherrima). The most popular ornamental and medicinal genera of this tribe are placed in Caesalpinia and Peltophorum [5].

• Gleditsiagroup • Acrocarpusgroup • Sclerolobiumgroup
• Gymnocladus*
• Gleditsia*		 • Acrocarpus • Sclerolobium
• Diptychondra
• Tachigali*
V.Peltophorumgroup • Caesalpiniagroup • Poeppigiagroup
• Vouacapoua*
• Bastesia
• Melanoxylon
• Recordoxylon
• Arapatiella
• Campsiandra
• Bussea
• Peltophorum*
• Schizolobium*
• Moldenhawera*
• Contzattia
• Parkinsonia*
• Delonix*
• Colvillea
• Lemuropisum
• Jacqueshuberia		 • Caesalpinia**
• Pterolobium*
• Moullava*
• Haematoxylum
• Stuhlmanna
• Stahli
• Zuccagnia*
• Cenostigma*
• Balsmocarpum
• Hoffmannseggia
• Stenodrepanum
• lophpcarpinia
   		 • Poeppigia
• Petrogynegroup VIII.Dimorphandragroup VIX.Orphanodendrongroup
• Petrogyne* • Erythrophleum*
• Pachyelasma
• Sympetalandra
• Mora
• Dimorphandra*
• Arcoa
• Burkea*
• Tetrapetrocarpon
• Childlowia
• Stachyothyrus		 • Orphanodendron

Table 1: List of genera arranged in the groups of caesalpinieae tribe [3].

Pharmacological Activities

Caesalpinieae medicinal plants, their extracts and their isolated compounds have demonstrated to have spectrum of biological activities as demonstrated in Table 2 [6-101].

Biological Activity Species Investigated Part(s) Pharmacological Effect Active Constituents Ref.
Antioxidant activity Pterolobiumhexapetalum Leaves, stem bark, flower and fruit The flower and fruit aqueous extracts (50µg/ml) showedsignificantantioxidant activity in vitro and effective free radical scavenging activity compared to control, The reducing ability showed at 1.352 and 1.326 absorbance with EC50 values 18 µg/ml in both flower and fruit aqueous extracts in compared to the standard ascorbic acid (19µg/ml). The fruit aqueous extract yielded highest amounts of phenols and flavonoids than other parts [6]
Moullavaspicata Leaves Acetone extract exhibited the highest total antioxidant activity and reducing power than hexane, methanol and chloroform extracts. However DPPH and ABTS scavenging activity were higher in methanol and acetone extracts respectively. Phenolic compounds, tannins and carbohydrates were present in all
The all plant extracts		  [7]
Gleditsiatriacanthos Leaves The methanol and ethyl acetate fractions exhibited antioxidant activity against DPPH-radical. Also, five isolated compounds were reported to have antioxidant activity (SC50 = 9.53, 11.67, 22.45, 98.44 and 58.91 µg/ml respectively). The methanol extract and ethyl the methanol and ethyl acetate fractions exhibited higher contents of phenols and flavonoids than the chloroform fraction. Also, five compounds were isolated from the chloroform and the ethyl acetate fractions and identified as caffeic acid, luteolin, iso-vitexin, apigenin-7-O-β-D-glucopyranoside and luteolin-7-O-β-D-glucopyranoside. [8]
Caesalpiniasappan Heartwood Protosappanin A and protosappanin B displayed greater inhibition of malondialdehyde and scavenging of hydrogen peroxide, while brazilein shows more scavenging of hydroxyl radicals. Protosappanin A, protosappanin B and brazilein [9]
Caesalpiniapulcherrima Flowers The methanolic extract exhibited a significant antioxidant activity against H2O2 induced oxidative stress in a goat liver model. The enzymatic antioxidants (catalase, peroxidase, superoxide dismutase, glutathione reductase and glutathione S-transferase) and the non-enzymic antioxidants (vitamins A, C, E and reduced glutathione) were significantly increased upon co-treatment with the flower extracts. Cassanediterpenes and flavonoids [10]
Caesalpiniadecapetala Wood Caesalpiniadecapetala extract exhibited a potent antioxidant activity which can play vital role against the diseases like neurodegenerative disorders, inflammation, viral infections and gastric ulcer. Gallic acid [11, 12].
Caesalpinia crista Leaves The methanolic extract (70%) exhibited potent antioxidant activity and ROS scavenging activity, as well asiron chelating property. For in vivo studies, it significantly increased in the level of superoxide dismutase, catalase, glutathione-S-transferase and reduced glutathione. The ethyl acetate extract showed a maximum free radical scavenging activity. The methanolic extract (100 mg) yielded 50.23 ± 0.003 mg/mL gallic acid equivalent phenolic content and 106.83 ± 0.0003 mg/mL quercetin equivalent flavonoid content. [13]
Peltophorumpterocarpum Leaves, barks and roots The plant parts exhibited significant free radical scavenging activity. The acetone extracts of roots and bark exhibited DPPH inhibition, yielding EC50 of 3.28 and 4.37 µg/ml, respectively as compared to 5.04 µg/ml exhibited by L-ascorbic acid. Quercetin-3-O-β-d-galactopyranoside [14, 15]
Caesalpiniadigyna Root The methanolic extract exhibited strong scavenging effect on DPPH free radical. Also, it exhibited a significant increase in the levels of catalase and superoxide dismutase activity, as well as a significant decrease in the levels of lipid peroxidation in serum, liver and kidney in a dose dependent manner, when compared to CCl4 treated control. Bergenin [16]
Burkea Africana Leaves The anti-oxidant activity was proved in  the methanol extract using DPPH-TLC fisetinidol-(4alpha--> 8)-catechin 3-gallate ,  bis-fisetinidol-(4alpha--> 6, 4alpha--> 8)-catechin 3-gallate, catechin, epicatechin and fisetinidol [17, 18]
Parkinsoniaaculeata Leaves The crude chloroform extract (71.7%) exhibited the most antioxidant activity which was more potent than standard gallic acid (83.5%). alkaloids, flavonoids, C-glycosides, terpenoids and saponins [19].
Pterogynenitens Stem bark The ethyl acetate fraction of the stem bark extract exhibited the strongest antioxidant activity, with IC50 values (µg/ml) of 2.10 ± 0.1 and 10.2 ± 0.3 on ABTS and DPPH, Myricetin, myricetrin, and quercitrin [20]
Anti-infective activity Caesalpiniaspinosa Pods The extract exerted the highest inhibitory activity against Staphylococcus aureus, followed by Pseudomonas fluorescens. Also, 3, 4, 5-tri-O-galloylquinic acid methyl ester was the most effective compound that assisted the antibacterial action of oxacillin as it intensified the susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin. Gallotannins [21, 22]
Caesalpiniacoriaria Leaves The fractions caused leakage of cellular materials (reducing sugar and proteins) through the membrane of Escherichia coli,Staphylococcus aureusand Klebsiella pneumonia. Also, these entered the inner membrane and inactivated the enzyme system (respiratory chain dehydrogenase) leading to inhibition of the respiration and growth of bacterial cells. Flavonoids and glycosides [23]
Caesalpiniaparaguariensis Bark The extract exhibited a significant inhibitory activity (MIC: 200 µg/mL) against Morganellamorganii, Erwiniacarotovora, Bacillus spp., Staphylococcus spp. and Enterococcus spp. ellagic and 3-O-methylellagic acids [24]
CaesalpiniaMelanadenia Aerial parts The hexane extract displayed antibacterial activity against all used bacterial and fungal strains. The most sensitive strains were Enterococcus feacalis(MIC=60 µg/mL), Streptococcus pneumoniae(MIC= 60 µg/mL), Staphylococcus epidermidis(MIC= 250 µg/mL), Enterobacteraerogenes(MIC= 250 µg/mL) and Criptococcusneoformans(MIC = 125 µg/mL) while the methanol extract didn't exhibit any activity. Flavonoids and triterpenoids [25]
Caesalpiniabonducella Seeds The methanol extract was reported to have a wide range of inhibiting activity against both Gram-positive and Gram-negative bacteria using the disc diffusion method. Triterpenoids (lupeol , lupeol acetate , β-amyrin  and α-amyrin) [26]
Caesalpiniasappan Leaves,  heart wood The ethanolic extract exhibited the highest inhibition zone [(34.0±2.7) mm] against Pseudomonas aeruginosa while petroleum ether extract showed inhibition zone [(6.0±0.3) mm] against Escherichia coli.
The methanolic extract of heart wood exhibited a strong growth inhibition of  Clostridium perfringens while it exhibited a weak growth inhibition of
Lactobacillus casei.		 Steroids, tannin, phenol, saponins and flavonoids
Bergenin(C-glycosyl benzoic acid)
homoisoflavonoids (4-O-methylsappanol, protosappanin A, brazilin and caeasalpin J).		 [27-31]
Caesalpiniaferrea Fruits The extract exhibited inhibitory activity against Candida albicans, Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis and Lactobacillus casei, with MIC values of 25.0, 40.0, 66.0, 100.0 and 66.0 µg/mL, respectively compared to chlorhexidine. However, low activity of extracts were reported in biofilm assay. Hydroxy phenols and methoxilated compounds [32]
Caesalpiniamimosoides Leaves The aqueous and ethanolic extract exhibit a potent antimicrobial activity against eight human pathogenic bacteria and six fungal strains Gallic acid [33]
Caesalpiniabonduc Seed coat and seed kernel For in vitro studies, the extracts exhibited antimicrobial activities, with MIC value of 22–350 µg/ml against methicillin resistant Staphylococcus aureus and ampicillin resistant Pseudomonas aeruginosa.  For in vivo studies, the hydro-alcoholic extracts of the seed kernel extract showed a significant antibacterial activity against Pseudomonas aeruginosawhere bacterialclearance from the lungs and less severe incidence of lung abscess were reported. Diterpenoids [34]
Delonixregia Leaves The ethylacetate fraction of ethanol extract (95%) exhibited excellent antibacterial activity against S. mitis (inhibition zone=19mm) and moderate activity against Lactobacillus spp. (inhibition zone=13mm). oleananoic acid [35]
Delonixelata Leaves The extract showed a significant inhibitory activity against Klebsiella pneumonia (MIC=18.40 ± 0.80 mg/ml) and Bacillus subtilis (MIC=17.60 ± 0.55 mg/ml). It showed moderate activity against Escherichia coli (MIC=15.00±0.37 mg/ml), Staphylococcus aureus (MIC=14.33±0.33 mg/ml), Salmonella typhi(MIC=14.33±0.74 mg/ml) and weak antibacterial activity against Salmonella paratyphi(MIC=12.17±0.17 mg/ml) and Proteus vulgaris (MIC=9.83±0.31 mg/ml). Phenolics and flavonoids [36]
Peltophorumafricanum root and stem bark The methanol extracts caninhibit both RNA-dependent-DNA polymerase activity of HIV-1 reverse transcriptase and ribonuclease-H activity of ribonuclease. Furthermore, water and methanol extracts of stem bark exhibited potent inhibitory activity against HIV-1 reverse transcriptase respectively, compared to Kaletra.
Furthermore, the butanol and ethyl acetate extracts showed inhibitory activity against HIV-1, CXCR4 (X4) and CCR5 (R5) tropic viruses.		 Gallotannins [37-40]
Peltophorumpterocarpum Flowers The extract exhibited the maximum inhibition zone against four Gram positive bacteria; Staphylococcus aureus , Bacillus cereus, Enterococcus faecalis and Streptococcus pyogenes and three gram negative bacteria; Proteus mirabilis,Acinetobacterbaumannii and Serratiamarsecens. Phenolic compounds, flavonoids, saponins, steroids, tannins, xanthoproteins, carboxylic acids, coumarins and carbohydrates [41]
Peltophorumferrugineum Flowers  The hexane, ethyl acetate, acetone and methanol were screened against Bacillus cereus, Staphylococcus aureus, Escherichia coli and Yersinia enterocolitica using agar dilution method. All the extracts showed antibacterial activity with MIC ranging from 0.1 to 1.25 mg/ml. This activity was mediated through the ability of these extracts to cause disintegration of cell wall, leakage of genetic material and inhibition of respiration of bacteria. Not mentioned [42]
Zuccagniapunctata Aerial parts The methanolic extract exhibited antimicrobial activity against Streptococcus pneumoniae with MIC values between 50 and 500 µg/ml.
Also,the extract (1 mg/mice) significantly reduced the number of viable Streptococcus pneumoniae in the lung.
The ethanolic extract was active against all assayed bacteria (Escherichia coli, Klebsiellapneumoniae, Proteus mirabilis, Enterobacter cloacae, Serratiamarcescens, Morganellamorganii, Acinetobacterbaumannii, Pseudomonas aeruginosa, Stenotrophomonasmaltophilia), with MIC values ranging from 25 to 200 µg/ml.The isolated essential oil exhibited a significant antifungal activity against the dermatophytes: Microsporumgypseum, Tricophytonrubrum and Tricophytonmentagrophytes with, minimum inhibitory concentration (MIC) values between 15.6 and 125 µg ml−1 where Tricophytonrubrum was the most susceptible species.		 2′,4′-dihydroxychalcone [43-45]
Parkinsoniaaculeata Leaves Different concentrations of chloroform extract of (50, 100, 250, 500 mg/ml) were assessedusing well diffusion method against some bacteria causing urinary tract infection (UTI) in humans. The chloroform extract showed a significant antibacterial activity against Escherichia coli with zone of inhibition 23±0.02 mm. The extract also inhibitory activity against Klebsiellapneumoniae,Staphylococcusaureus, Staphylococcus chonii, Proteus mirabilis and Pseudomonas aeruginosa compared to streptomycin ,reporting that Parkinsoniaaculeata was active against UTI causing bacteria. Apigenin ,vitexin, iso-vitexin,orientin, iso-orientin, chrysoeriol. [46]
Gymnocladuschinensis Seeds Gymnin was reported to exert antifungal activity toward the fungal species Fusariumoxysporum (IC50 = 2 µM) and Mycosphaerellaarachidicola (IC50 = 10µM). Gymnin [47]
Moldenhaweranutans Stems The chloroform extract exhibited anti HIV activity (72%) at concentration of 200 mg/ml using human immunodeficiency virus-reverse transcriptase (HIV-1 RT) assay. Diterpenes [48]
Anti-inflammatory activity Caesalpiniaparaguariensis Stem bark The extract components exhibited the best enzyme inhibitors of Hyaluronidase (Hyal) and inducible Nitric Oxide Synthase (iNOS)., reaching the 90% inhibitory concentration (IC90) values ranging from 2.8 to 16.4 µM. Phenolic lactones (ellagic acid, 3-O-methylellagic acid, 3, 3'-di-O-methylellagic acid and 3,3'-di-O-methylellagic-4-β-D-xylopyranoside) [24]
Caesalpiniasappan Heartwood The extract components exhibited  anti-inflammatory activity through inhibition of the induction of iNOS m-RNA in a dose-dependent manner. The synthesis of these transcripts at the transcriptional level was attenuated and NO activity was decreased. Caesalpiniaphenols [49]
Caesalpiniabonducella Seeds The seed oil significantly reduced the paw oedema volumes in experimental rats compared to that of control. Seed oil [50]
Caesalpiniamimosoides Roots Crude chloroform and acetone extracts showed potent nitric oxide inhibitory activity, with IC50 values of 11.0 and 21.6 µg/ml, respectively. Diterpenes [51]
Caesalpiniapulcherrima Aerial parts The extract  components significantly inhibited the inflammatory mediators; nitric oxide (NO), and cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-12 in dose-dependent manner. Five flavonoids (5, 7-dimethoxyflavanone, 5, 7-dimethoxy-3′, 4′-methylene dioxyflavanone, isobonducellin , 2′-hydroxy-2, 3, 4′, 6′-tetramethoxychalcone and bonducellin) [52]
Burkeaafricana Leaves The methanolic extractsignificantly reduced rat paw oedema where dose of 40mg/kg inhibited the inflammation by 88.5%, compared to ketoprofen (10mg/kg) which produced 69% inhibition of inflammation at the same hour. Alkaloids, cardiac glycosides, flavonoids, tannins, saponins, steroids and terpenoids [17]
Erythrophleumsuaveolens Stem bark The methanolic extract (100 mg/kg) exhibited approximately 47% inhibition of carrageenin-induced paw oedema 1 h after administration and reduced the sensitivity to pain by 30%. The ethyl acetate fraction produced over 33% inhibition of carrageenan-induced paw oedema through inhibition of 5-lipoxygenase. Alkaloids and procyanidins [53]
Cytotoxic, Antitumor and Anticancer activities CaesalpiniaSappan Heart wood The ethylacetate extract exert inhibitory activities on growth-related signaling and cell mitosis Three major compounds were reported for different antitumor activities, demonstrating that sappanchalcone blocked cell cycle progression in the G2/M phase, brazilin inhibited TNFα/NF-κB signaling, while butein inhibited IL-6/STAT3 signaling, and TNFα/NF-κB signaling. The anti-tumor efficacy of the extract was better than the individual compounds acting alone as the extract contained multiple active compounds with different antitumor activities which could be additive to enhance the total antitumor activity of the extract. Sappanchalcone, brazilin, and butein [54]
Seeds The extract compounds exhibited significant cytotoxicity against a human pancreatic cancer cell line (PANC-1). Three new cleistanthanediterpenes (tomocinon, tomocinol A and tomocinol B) [55]
Hear wood The anticancer activity of, a compound isolated from Caesalpiniasappanwas evaluated against human breast cancer MCF-7 cells. brazilein inhibited growth of breast cancer cells , with an IC50 value of  7.23 ±  0.24 µmol/l. brazilein acted through downregulation of GSK-3β/β-catenin, which resulted in a  downregulation of cyclin D1 and   a blockage of the cell cycle in G1 phase . Blockage was concentration-dependent .This was confirmed by western blot and reverse transcription polymerase chain reaction (RT-PCR) assay. brazilein [56]
Caesalpiniabonduc Leaves The ethanolic extract components displayed a significant inhibitory activity antiproliferative activity against MCF-7 (breast adenocarcinoma), DU145 (prostate carcinoma), C33A (Cervical carcinoma) and Vero (African green monkey kidney fibroblast) cells; compared with staurosporine (a broad spectrum inhibitor of protein kinases) was used as a positive control. Cassanediterpenes (caesalpinolide-C, caesalpinolide-D, caesalpinolide-E and one cassanefuranoditerpenes) [57]
The methanol extract was evaluated for antitumor activity against Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. The extract significantly reduced the tumor volume, packed cell volume, and viable tumor cell count in a dose-dependent manner as compared to that of the EAC control group confirming antitumor activity. Diterpenes [58]
Erythrophleumfordii Leaves The extract compounds were assessed against a panel of human cancer cell lines (A549, MCF-7, PC-3 and HepG2). Erythrophlesin H displayed potent cytotoxic activity against all the cell lines in a dose-dependent manner, with IC50 values of 24.5, 17.2, 12.5 and 25.2 µM respectively, comparing with camptothecin, which has IC50 values ranging from 0.54 to1.02 µM against all kind of cancer cell lines. Prostate cancer cells (PC-3) were the most sensitive cells to erythrophlesin H through induction of apoptosis. two new cassainediterpenoid–diterpenoid amide dimers (erythrophlesins H and erythrophlesins I) [59]
Gleditsiacaspica Fruits The cytotoxic activities of four caspicaosides were assessed against the three human tumor cell lines HepG2, A549 and HT29 Caspicaosides B and C exhibited a significant cytotoxic activities against the cells (IC50 =1.5–6.5 µM).  Caspicaosides A and D exhibited significant cytotoxic activities on HepG2 cell line (IC50 = 4.5 and 5.4 µM, respectively), and IC50>10 µM against the other two cell lines. The cytotoxic activity was dependant on the number of monoterpene units which caspicaosides bears. Triterpenoid saponins (four caspicaosides A-D) [60]
Hepatoprotective activity Delonixregia Leaves The methanolic extract exhibited hepatoprotective activity against CCl4-induced liver injury. the plant extract significantly reduced AST, ALT and ALP, as well as total and direct bilirubin in a dose dependent manner.   Kaempferol 3-rhamnoside , Quercetin 3-rhamnoside , Kaempferol 3-glucoide , Kaempferol 3-rutinoside , Kaempferol 3-neohesperidoside , Quercetin 3-rutinoside and Quercetin 3-glucoside [61]
flowers The ethanolic extract showed hepatoprotective activity against CCl4- induced hepatic cell damage. A significant decrease in the enzyme levels (ALT, AST and ALP) were observed regarding their respective normal values which indicated stabilization of the hepatocyte cell membrane as well as repairing of hepatic tissue damage caused byCCl4. This liver protection ability was attributed to the presence of flavonoids with their efficient free radical scavenging .This study suggested use of Delonixregia flowers as chemopreventive agent against two main causes of liver damage: liver toxicity by chlorinated agents and liver cancer. Flavonoid (quercetin, quercitrin, isoquercitrin and rutin) [62,63]
Caesalpinia crista Leaves The methanolextract displayed ameliorating effect on iron-overload induced liver injury in mice where it  attenuated liver iron and serum ferritin levels compared to control group. Also, the extract inhibited lipid peroxidation, protein oxidation, and liver fibrosis in a dose dependent manner and decreased the serum liver enzymes. Furthermore, it enhanced the levels of liver antioxidant enzymes and exhibited DPPH radical scavenging and protection against Fe2+-mediated oxidative DNA damage. The hepatoprotective effect of the plant extract against the model hepatotoxicant iron overload was mediated through its potent antioxidant and iron-chelating properties. Phenolics and flavonoids  [64]
Caesalpiniabonducella Leaves The methanolic extract produced significant hepatoprotective effects against CCl4-induced liver injury in Wister albino rats by decreasing the activity of serum enzymes (AST, ALT and ALP), bilirubin, uric acid, and lipid peroxidation. and significantly increased the levels of superoxide dismutase , catalase , glutathione , vitamin C, vitamin E and protein in a dose-dependent manner. Phenolics [65]
Anti-diabetic and hypoglycemic activity   Caesalpiniaferrea Stem bark The aqueous extract established hypoglycemic properties in streptozotocin-induced diabetic rats. It reduced blood glucose levels and improved the metabolic state of test animals through the regulation of glucose uptake in liver and muscles by way of Akt activation, restoring the intracellular energy balance confirmed by inhibition of AMPK activation. Chalconetrimer (pauferrol A) and two chalcone dimers (pauferrol B and pauferrol C) 
di-O-glycosyl-C-glucosyl flavones: isovitexin 2″-O-β-[xylopyranosyl-(1″″→2″)-O-β-xylopyranosyl]; Vitexin 2″-O-β-[xylopyranosyl-(1″″→2″)-O-β-xylopyranosyl]; Orientin 2″-O-β-[xylopyranosyl-(1″″→2″)-O-β- xylopyranosyl		 [66]
Caesalpinia crista Seed kernel The ethanolic and aqueous extracts lowered the blood glucose level in the alloxan-induced diabetic albino rats. The ether extract showed a marginal antidiabetic activity, while the petroleum ether extracts show no activity. Furthermore, the studies showed that the hypoglycemic activity may be partly due to positive effects on glycogen synthesis in the liver, skeletal muscle and heart muscle due to the insulin-like action of its constituents and may be partly due to stimulatory action on insulin release. Triterpenoidal glycosides [67,68]
Caesalpiniabonducella Seeds Oral administration of the extract (300 mg/kg) provided significant antihyperglycemic action in alloxan -induced hyperglycemia model through blocking of glucose absorption. Also, the extracts significantly lowered the elevated cholesterol and low density lipoprotein level in diabetes induced hyperlipidemia providing antihyperlipidemic action. Not mentioned [69]
Gastroprotective activity   Caesalpiniapyramidalis Inner bark The ethanol extract significantly inhibit the ulcer lesion index, the total lesion area, and the percentage of lesion area in dose-dependent manner in the ethanol-induced ulcer model. Also, it reduced the ulcer index in the indomethacin-induced ulcer model. However, in the ligature pylorus model, the extract failed to significantly change the gastric secretion parameters, although, there was a significant increase in mucus production. Furthermore, the extract inhibited Helicobacter pylori growth, with inhibition zone of 12.0±1.7 mm at 625µg/ml. Phenolic compounds [70]
Cenostigmamacrophyllum  Leaves The gastroprotective activity of hydroalcoholic extract was established through different gastric ulcer models in rodents as absolute ethanol, HCl/ethanol, ischemia-reperfusion, cold restraint stress and indomethacin-induced ulcers. The extract inhibited the ulcer lesion in all four models in dose- dependent manner. Also, it increased catalase activity, but couldn’t protect the gastric mucosa against indomethacin-induced lesions. The gastro protective activity was mediated throughnitric oxide release, KATP channels opening and antioxidant activity. Gallic acid, methyl gallate, ellagic acid, quercetin, quercetin-3-O-β-D-glucopyranoside, quercetin-3-O-(6"-O-galloyl)-β-D-glucopyranoside (tellimoside), quercetin-3-O-(6"-O-E-p-coumaroyl)-β-D-glucopyranoside (helichrysroside), agathisflavone and vitexin [71]
Analgesic activity Caesalpiniapyramidalis Inner bark The ethanolic extract inhibited acetic acid-induced visceral pain, capsaicin-and glutamate-induced pain. The antinociception caused by the ethanol extract in the abdominal constriction test was significantly attenuated by intraperitoneal treatment of mice with l-arginine. The extract produced dose-related antinociception in several models of pain through mechanisms that involved both glutamatergic system and/or the l-arginine–nitric oxide pathway, supporting the folkloric usage of the plant to treat various painful processes. Flavonoids, phenols, saponins, steroids, tannins, and triterpenes [72]
Caesalpiniavolkensii Root bark The chloroform and ethyl acetate extracts (100 mg/kg)showed asignificant reduction in the number of writhing episodes induced by acetic acid and increased pain latency threshold in hot-plate test compared to control. Cassanefuranoditerpenes [73]
Caesalpiniabonducella Flower The extract exhibited a significant antinociceptive effect in the inflammatory phase of formalin-induced pain and acetic- induced parietal pain. Glycosides and terpenoids. [74]
Cenostigmamacrophyllum Stem bark and leaves Bergenin, isolated compound , produced a significant and dose-related inhibition of acetic acid-induced abdominal constrictions in mice compared to indomethacin; a standard NSAID. It was proved for the first time that the systemic administration of bergenin produces a dose-related analgesic activity. Bergenin [75]
Delonixelata Leaves Theextract produced a significant dose-dependent antinociceptive activity in acetic acid –induced abdominal writhing and tail flick models. For the writhing test, a dose at 300 mg/kg significantly inhibited (74.94%) the nociception induced by acetic acid, but was less effective than acetylsalicylic acid (84.06%). The tail-flick test showed that the extract showed greater efficacy compared with increase in the latency to response of tail to the thermal stimulation in a dose dependent activity. Alkaloids, tannins, triterpenoids, steroids
and glycosides		 [76]
Burkea Africana Leaves The methanolic extractsignificantly and dose dependently inhibited acetic acid-induced abdominal contractions in mice at doses tested (20-80mg/kg body weight compared to ketoprofen (10mg/kg), a standard non-steroidal analgesic drug. Alkaloids, cardiac glycosides, flavonoids, tannins, saponins, steroids and terpenoids [17]
Effects on the nervous system Caesalpiniasappan Heart Wood The extract compounds effectively inhibited BV-2 microglia-mediated release of  neuroinflammatory mediators including nitric oxide (NO),  prostaglandin E2(PGE2 ), tumor necrosis factor (TNF-α), interleukin-6( IL-6) and reactive oxygen species (ROS). DSB also markedly protected neurons against inflammatory microglia-mediated neurotoxicity in a microglia–neuron co-culture system through the blockage of two major neuroinflammation-related signaling pathways [IKK-Iκ B-nuclear factor kappaB (NF-κB) and p38/ERK mitogen-activated protein kinase (MAPK) cascades] which lead to suppression of neuroinflammatory mediators ׳ production.This confirmed theanti-neuroinflammatory and neuroprotective properties of theextract. Homoisoflavone compound;deoxysappanone B [77]
Caesalpinia crista Seed kernels The aqueous extract significantly ameliorated the amnesic effect of scopolamine in mice compared to standard drug piracetam.  It confirmed that the extract could potentiate the learning and memory process and improve cognition in disorders like dementia and various neurodegenerative disorders. Terpenoids [78]
leaves Theaqueous extract exhibited anti-amyloidogenic potential as it prevented the formation of amyloid beta from monomers and fibrils aggregation from oligomers. Furthermore, the extract was able to dis-aggregate pre-formed fibrils, indicating that Caesalpinia crista leavesmay be a candidate for Alzheimer's disease therapeutics. Terpenoids [79]
Caesalpiniabonducella Seeds The extract (600 and 800mg/kg ) showed significant anti-convulsant and anxiolytic activities in maximal electro shock, strychnine - and picrotoxin-induced convulsions models. Saponins, proteins, homoisoflavone (bonducellin), carbohydrates and sterols [80, 81]
Effects on immune system Dimorphandramollis Seeds granulocytopoietic activity of DMTI-II (Dimorphandramollis trypsin inhibitor) was established through activation of allergen-induced neutrophil and eosinophil mobilization from bone marrow to lung tissues. DMTI-II (23-kDa trypsin inhibitor purified from Dimorphandramollis seeds) [82]
Caesalpiniasappan Heart wood The  ethanol extractinhibited the proliferation of T lymphocyte and B lymphocyte. Also, Brazilein suppressed the mice humoral immune response which was confirmed with a plaque forming cell test. Furthermore, immune organs (thymus and spleen) in mice treated with brazilein were notably atrophied and weight loss was observed in vivo (intraperitoneal injection).  The immunosuppressive activity of brazilein was attributed to the induction of apoptosis in the mice spleen lymphocytes. This study provided a scientific basis for the applicability of Caesalpiniasappan in Chinese medicines for treating a variety of immune-mediated pathology. Brazilein [83]
Caesalpiniabonducella Seeds The aqueous extract of displayed effects on the cell mediated and humoral components of the immune system. The extract (400mg/kg) could significantly increase hemagglutinating antibody titer and change the delayed type hypersensitivity proving. Thus, the extract could be a promising immunostimulatory agent. Saponins , homoisoflavone (bonducellin), carbohydrates and sterols [84]
Effect on cardiovascular system Moldenhaweranutans   The methanolic extract compounds produced dose-dependent hypotensive and tachycardiac effects in both conscious and anesthetized rats. The tachycardia is mediated reflexly through inhibition of vagal and activation of sympathetic drive to the heart. The hypotension is mainly due to withdrawal of sympathetic tone to the vasculature and also partly to an active vascular relaxation. a labdenicditerpene; Labd-8 (17)-en-15-oic acid (Labd-8) [85]
Caesalpiniasappan Heart wood The methanolic extract significantly and dose-dependently relaxed α1-receptor agonist phenylephrine-precontracted aortic rings in isolated rat thoracic aorta without affecting passive tension of these vessels.  Similar vasorelaxant effects were observed with brazilin and hematoxylin (isolated compounds). Therefore, this study confirmed that brazilin and hematoxylin may be responsible for the vascular relaxant effects ofCaesalpiniasappan, via endogenous NO and subsequent cGMP formation. Brazilin and hematoxylin [86]
Anti-hyperlipidemic activity Gleditsiasinensis Fruits The aqueous extract improved  lipid profile, including triglycerides , total cholesterol and low density lipoprotein cholesterol was determined. it significantly decreased the lipid levels of serum, aorta and liver, attenuated aortic atherosclerosis and improved aortic remodeling without liver and muscle toxicity. Phenolic compounds including ethyl gallate and caffeic acid and five flavonoids including dihydrokaempferol ,eriodictyol , quercetin , 3,3',5',5,7-pentahydroflavanone and (-)-epicatechin [87]
Anti-arthritic effect Caesalpiniasappan Heartwood The anti-arthritic activity of an ethanol extract was evaluated using collagen-induced arthritis (CIA) in Wistar rats. It markedly attenuated collagen-induced arthritis and levels of the proinflammatory cytokines interleukin-1 beta, interleukin-6, tumor necrosis factor alpha and prostaglandin E2  in blood, and expression of cyclooxygenase-2 and transcription factor NF-κB p65 in the paw of CIA rats. Terpenoids [88]
The anti-osteoarthritic effects of ethanolic extract were assessed on human chondrocytes and macrophages. It inhibited the expression of pro-inflammatory cytokines IL-1β and TNF-α in IL-1β-stimulated chondrocytes and LPS-stimulated THP-1 macrophagesin dose dependant manner.
Furthermore, The extract suppressed the synthesis of NO in primary osteoarthritic chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. The extract can effectively abrogate the IL-1β-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-κB (p65/p50) signaling. Blockade of IL-1β-induced NF-κB signaling and its downstream pro-inflammatory, targeted by the extract, may be beneficial for reducing cartilage breakdown in arthritis.		 Terpenoids [89]
Anti- filarial activity Delonixelata Leaves and seeds The repellent activity of hexane, ethyl acetate, benzene, chloroform and methanol extract was evaluated against Culexquinquefasciatus (the mosquito vector of filariasis.) The applied plant crude extracts protected against mosquito bites without any allergic reactions. The repellent activity of the extract was dependent on the strength of the extract. Among the tested solvents, the leaf and seed methanol extract showed the maximum efficacy. Phenolics  and flavonoids [90]
Caesalpiniabonducella Leaves The crude extract showed gradual fall in microfilariae (mf) count in Litomosoidessigmodontin-cotton rat model (95%). It also exhibited macrofilaricidal (96%) and female sterilizing efficacy (100%) in adult worms. The butanol fraction reduced mf count (73.7%) and caused 82.5 % mortality in adult worms with female sterilization (100%). The aqueous fraction exerted microfilaricidal activity (90%) and worm sterilization (100%). The hexane fractions exhibited macrofilaricidal activity (64% and 95%) and caused gradual fall in microfilaraemia with worm sterilization. For Brugiamalayi-coucha model, the hexane fractions showed gradual reduction in microfilaraemia and caused sterilization of female parasites (80%). Terpenoids [91]
Anti-malarial activity Caesalpinia crista Seed kernel Most of the isolated diterpenes showed antimalarial activity with norcaesalpinin E showing the most potent activity. Indeed, it was more potent than the standard antimalarial drug chloroquine. Diterpenes (44 cassane- and norcassane type diterpenes) [92]
  Caesalpiniavolkensii Root bark The ethyl acetate extract exhibitedantiplasmodial activity. Cassane furanoditerpene [73]
Wound healing activity Poincianellapluviosa(Caesalpiniapluviosa) Stem bark The wound-healing properties of hydro alcoholic extract were established on HaCaT- keratinocytes cell line and human primary dermal fibroblasts (pNHDF). The extract increased mitochondrial activity and proliferation of keratinocytes and dermal fibroblasts.  Two phenolic compounds, ethyl gallate and rhuschalcone , lupeol, betulinic acid and stigmasterol [93]
Anthelmintic activity Peltophorumafricanum Stem bark and leaves The acetone extracts exhibited ovicidal and larvicidal activity against Haemonchuscontortus, with notable complete lyses of larva at a concentration of 5 and 25 mg/ml. Furthermore, the water extracts showed this effect at a concentration of 0.5 mg/ml after 24 h against cestodes of Hymanolepsisdiminuta, while the water extracts had an effect against H. diminutaat a concentration of 25.4 mg/ml after 1 h. Terpenes, xanthone and coumarins,benzenoids, flavanols, flavonols, condensed flavonoids, gallotannins and δ-lactones  [94, 95].
Caesalpinia crista Bark The anthelmintic activity of an aqueous methanolic extractwas investigated against sheep trichostrongylid nematodes.  For the in vivo study, the bark extract (1.0–3.0 g/kg) exhibited dose- and time-dependent anthelmintic effects by causing mortality of the worms and inhibition of egg hatching. Caesalpinia crista showed LC50 of 0.134 mg/mL in egg hatch test. Maximum reduction in eggs per gram (EPG) of faeces was recorded with Caesalpinia crista (93.9 %) at 3.0 g/kg on 13th day and 5 post-treatment compared to the positive control levamisole (7.5 mg/kg) which showed 95.1–95.6% reduction in EPG.These data prove that Caesalpinia crista possesses anthelmintic activity in vitro and in vivo justifying their use in the traditional medicine system of Pakistan.   [96]
Amoebicidal Activity Parkinsoniaaculeata Roots Different doses of isolated rotenoids (rotenone, elliptone and deguelin) from roots in vitro were screened for anti-amoebic activity against Entamoebahystolytica The rotenoid recovery of the plant parts has been observed as per the order: root> stem>leaves> pods>seeds. The isolated plant rotenoids showed a significant antiamoebic activity at a dose of 500 mg/l, compared to 250 mg/l of used standards (rotenone and derris acid). However; they showed low antiamoebic activity, compared to the standard antiamoebic drug (metroindazole) was effective at 8 mg/l dose. rotenoids (rotenone, elliptone and deguelin) [97]
Anti-fertility effect Caesalpiniapulcherrima Leaves The antifertility potential of the ethanolic extract of leaves was assessed in two experimental animal models (anti-implantation and estrogenic/antiestrogenic activity) in female mice by observing number of implants, estrus cycle, vaginal cornification, uterus weight and cholesterol content. A good anti-implantation (66.66 %) activity in female mice was observed at all the tested dose levels .The extract significantly increased the uterine weight and cholesterol content in immature mice. Simultaneous administration of the extract along with ethinyl estradiol showed significant estrogenic activity. Terpenoids [98]
Anti-estrogenic activity Caesalpiniabonducella Seeds Graded doses of the methanolic extract caused follicular degeneration in ovary, vacuolation, mild disorganization of uterus and inhibition of estrous cycle duration and mean ovarian weight .The antiestrogenic property of CBSE is mediated through via inhibition of estrogen secretion. Homosoflavonoids [99]
Antipsoriatic activity Caesalpiniabonduc Leaves The hydroalcoholic extract ofleaf and its fractions were established for antipsoriatic activity in Swiss albino mice.  A butanol fraction of Caesalpiniabonduchydroalcoholic extract (CBHAB) and water fraction of Caesalpiniabonduc hydro alcoholic extract (CBHAW) produced significant orthokeratosis. In relative epidermal thickness, a significant reduction with respect to control was observed in groups treated with retinoic acid, butanol fraction of Caesalpiniabonduc decoction (CBDB) and water fraction of Caesalpiniabonduchydroalcoholic extract (CBHAW). Also, CBHA showed the maximum antiproliferant activity (IC50= 77.5±12.7 µg/ml).   [100]
Anti-Diuretic activity Delonixregia Flowers The methanolic extract (100 and 200mg/kg) exhibited a significant diuretic activity with increased urine volume and electrolyte excretion when compared to positive control furosemide (20mg/kg, orally). Tannins , phenolic compounds, flavonoids and phytosteriods [101]

Table 2: The biological activities of different species belonging to caesalpinieae tribe and their reported pharmacological effects.

Conclusion and Discussion

The present review summarizes documented pharmacological properties of different extracts of the plants that fall under Caesalpinieae tribe. The most popular medicinal plants in this tribe are mainly found in 3 genera: Caesalpinia, Peltophorum and Delonix. Further clinical and pathological studies are required to investigate the active potential of bioactive compounds of the medicinal plants of this tribe. Furthermore, there is a scope for research to establish lead compounds from these plants for drug development. This information will be helpful for pharmacognosists, ethnobotanists, botanists and pharmacologists.

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Citation: El-Nashar HAS, Eldahshan O, Singab AN (2015) The Tribe Caesalpinieae (Fabaceae): An Updated Review on Pharmacological Aspects. Med Aromat Plants 4:215.

Copyright: © 2015 El-Nashar HAS, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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