Phytochemical Profile and Pharmacological Activities of Karanjawa (Caesalpinia bonducella L.): An Important Botanical Origin Drug of Unani System of Medicine

Introduction

Natural sources like plants (Nabatat), animals (Haiwanat), and minerals (Zamadat) have been used for healing from the prehistoric to the historic period of human development. Advancement in disease management evolved step by step with the development of almost all civilizations. In the present world, several phytochemicals isolated from plants with their pharmacological activities such as Atropine, Aspirin, Digoxin, Ephedrine, Morphine, Reserpine, Quinine, and Tubocurarine are being used in conventional medicine effectively to manage various ailments. The world has taken interest in natural remedies and accepted them for managing pathological conditions of humans after evaluating phytopharmacological activities on scientific parameters.¹ Biologically active compounds produced by plant tissues as primary and secondary metabolites with some therapeutic activities are called phytochemicals. They may be categorized as alkaloids, lipids, glycosides, flavonoids, phenolics, saponins, tannins, essential oils, steroids, and other compounds.²

Karanjwa is a well recognized botanical origin drug used by Unani physicians for a long time for the prevention and treatment of variety of ailments. It posseses numerous therapeutically active substances like Bonducin, bonducellpins (A, B, C, and D), caesalpinin, caesalpinianone, α, and β-caesalpin, 6-Omethylcaesalpinianone, noncrystalline, diosgenin, steroidal, saponins, hydrocarbons, fatty Acids, amino acids, glycoside, and terpenoids. The   medicinal herbs have   numerous   pharmacological   activities due to the presence of these compounds such as immunomodulatory activity, antioxidant activity, anti- inflammatory activities, antiallergic, hypoglycemic activity, hypolipidemic activity, adaptogenic activity, antimicrobial activity, antidepressant activity, anti- infertility activity, antitumor activity, antiulcer activity, aphrodisiac activity, and hepatoprotective activity.³

The Unani system of Medicine is based on the teaching framework of Buqrat (Hippocrates) and Jalinoos (Galen), also known as Greco-Arab Medicine. It originated in Greece and developed in Arab as a medical science.⁴ Ilaj bi’l-Dawa is the most popular method that includes several Mufrad Advia (single drugs) and Murakkab Advia (compound drugs) to prevent and cure disease successfully.^5-7 Karanjwa is a well renowned Mufrad Advia of botanical origin that is used by Unani physicians either single or in combination with others. Advia in the management of various ailments viz. Humma (Fever),^8-13 Zeequn Nafas (Asthma),^8,10,12-15 Waram (Inflammatory swelling),^8,12,16 Uqr (Infertility),^8,12 Qeela-i-Mayya (Hydrocele),^{8,10,12-15,17} Kharis (Itching),^8,10,16,17 Ulcers,^8,10,16 Istisqa,^10,12-14,17 Qulinj Reehi,^10-13,18 Amraz Barida Dimagiya,¹² Iltihab Mufasil,^10-13 and Muqawwi Basar.¹⁶ The pharmacological action of Karanjwa has been mentioned in Unani literature by the reputed physician of Unani system of Medicine (USM) as Anti-inflammatory^{8,11,13-16,19} Anti-coagulant,^8,11,16,19 Antiseptic,^8,10,13,17 Antipyretics,^{8,10,14,17-19} Anti-malaria,^15,17 Expelled Morbid Matter,^8,10 Blood purifier,^13,17 Tonic,⁸ Carminative,^8,10,16,19 Emmenagogue,⁸ Desiccative,^10,13-17 Absorbent,^13-17 Wormicidal,^10,17,19 and Anti-spasmodic.^10,13,14,17 The seed kernel of Karanjwa is also an important content of several compound formulations Habb-e-Mubarak, Majoon-e-Gajgah,¹⁶ Habb-e-Karanjwa,^12,13,16 Jawarish Gachgah,^14,15,16 Ikseer Humma,¹⁴ and Habb-e-Rab’a.^13,15

The Unani literature reports use of Karanjwa in several disease conditions like Humma (Fever), Amraz-i-Dimag (Nervine Disease), Amraz-i-Dahen (Oral disease), Amraz-i-Sadar (Chest disease), Amraz Mida-wa- A’ama (Gastrointestinal disease), Amraz Kabid (Liver disease), Amraz A’aza Baul (Urinary disease), Amraz- i-Tanasuliya (Reproductive disease), and Amraz-i-Jild (Skin disease) as mentioned in the text of USM.^8-19 Therefore seed kernels and other parts of Karanjwa are used in the disease of several systems of the body in both traditional as well as the conventional system. Available information on Karanjwa is very sparse. So, an attempt has been made to compile the available information on the phytochemical and pharmacological activity of Karanjwa and its various formulations to highlight the therapeutic potential of this widely known drug.

Material and Methods

The present review was undertaken to analyze the existing data about the drug Karanjwa with detailed information on conventional uses especially in the Unani system of medicine, with its phytochemical constituents and reported pharmacological actions. Various authentic databases including classical and contemporary texts, indexed journals have been reviewed and conclusions have been drawn.

Observation and Discussion

Description of Karanjwa

Karanjwa is a fruit of Khardar Bail (thorny shrub) described by ancient Unani physicians in their texts. It is found in all parts of India, especially in Bengal and Burma.^{8,11,12,14,16,18,19} The plant has dark-grey branches that bear tough, straight, and yellow prickles. The leaf of Caesalpinia bonducella is about 30–60 cm long, branched, and has thorny petioles. The leaf has 6 to 8 sets of pinnates with two stipulary spines. The plant has short pedicles and exhibits thick yellow or red blooms of 15-25 cm long with axillary racemes. The pod is an elongated vessel of 5 to 7.5 cm in length with 2 to 3 seeds. The seeds are very much similar to the eyeball and bear hard greenish or grey coats with a small pit. The inner center part of the coated seed is known as the seed kernel.^8,12,20-22

Distribution of Karanjwa

Karanjwa (Caesalpinia bonducella) is a perennial shrub of the family Caesalpiniaceae that is found in all parts of the world viz. India, Pakistan, Sri Lanka, and Andaman and Nicobar islands.^3,12,14 In India, the plant habitats in Himalayas and plains parts up to 1000 altitude. It is also densely populated in the deltaic region of southern, eastern, and western India. The plant of Karanjwa is cultivated as a bar for crop fields in several regions.^8,22

Ethnomedicinal uses of Karanjwa

Ethnomedicine is sometimes also known as traditional medicine. It is an area of anthropology that studies different cultures, illnesses, and ideas of health. It includes how individuals think, and how individuals act about prosperity and healing.²³ Ethnomedicinally, Karanjwa was used by Unani physicians for a long time in several adverse conditions viz., especially in fever. Powder of seed kernel of Karanjwa with equal quantity of Filfil Siyah is placed into a bottle for 15 days, after which 15–30 grains per day are used in Humma (fever).⁸ Seed kernel of Karanjwa (2-6 gm) in powder form also reduces the severity of the fever. Shivering episodes subside after using nasal drops prepared from seed kernel with water.¹² A formulation of Seed Kernel of Karanjwa, Dar Filfil (Piper longum), and Honey was used in Tap Kuhna (Chronic Fever).^12,16,19 Leaf of the Karanjwa plant along with Filfil Siyah (Piper nigrum) 21 pieces is used in Chothiya Bukhar (Quartan fever).^8,12 Root-bark of Karanjwa plant (5 ratti) in powder form is used to treat Nobati Bukhar (episodic fever).⁸ Decoction of root- bark or leaf along with branches of Karanjwa plant is also used in Nobati Bukhar.¹² Powder of Seed Kernel of Karanjwa, Plaspapda muqassar (Butea frondosa), and Kumple Babule (Vachellia nilotica) in equal quantity is also used in Nobati Bukhar (episodic fever).^10,17 Seed Kernel of Karanjwa powder in dose of 2-5 ratti is used in Nabati Bukhar^10,15 and 5-10 grains are used in post febrile illness.^8,12 Root-bark or Seed Kernel of Karanjwa plant and Filfil Shiya in equal quantities is used during shivering episodes.¹⁷ Karanjwa leaf and Filfil Siyah mix together is used to stop shivering, and Amraz Fasad-i-Khoon,^10,17 Amraz-i-Dimag (Nervine disease) viz. Falij (Paralysis) and Laqwa (Facial Paralysis) are managed through the external and internal use of Karanjwa. A’ab Berg-i-Karanjwa is burnt in oil till the content of water is vaporized and following this, Dalak (massage) is performed in Nervine disease.^8,12 Karanjwa plant is also used in Amraz-i-Dahen (Oral disease); the seeds of Karanjwa are burned till outer coats turn black, then powdered with Phitkari (Alum) to form tooth powder for use in Waram Lissa (Gingivitis).¹² A tooth powder prepared by ash of Seed Kernel of Karanjwa, Supari (betel nut), and Phitkari is also used in gum inflammation, and mouth ulcers.⁸ Amraz-i-Sadar (Chest disease) like Zeequn Nafas is treated by the powder of Seed Kernel of Karanjwa which is prepared through the burning of Karanjwa seed (3-pieces) in the fire to remove the outer coat.^{8,12,10,15,17} 

The Unani physicians also treat Amraz Mida wa A’ama through Seed Kernel of Karanjwa. Powder of Seed Kernel of Karanjwa along with jaggery is used in Deedan-i-A’ma (Intestinal Worm).^8,12,17 Seed Kernel of Karanjwa with Bawbarang (Embelia ribes) is also used to kill Deedan-i-A’ma.¹² Hookah (A pipe with a long, flexible stem arranged such that smoke is cooled by passing through water) of Seed Kernel of Karanjwa is used in the treatment of pain due to flatulence (Qolinj Reehi). Seed Kernel of Karanjwa and Heeng (Asafoetida) powdered in boiled milk is used in indigestion.8,12 Powder of Seed Kernel of Karanjwa (1/2 pieces) and Laung (seven pieces) is also used in Qolinj Reehi.^10,12 Powder of Seed Kernel of Karanjwa (1/2 piece) and Filfil Shiyah (five pieces) is also used in Dard-i-Qolinj.^16,19 In Amraz-i-Kabid, different parts of the Karanjwa plant are used by the ancient Unani physicians. A’ab berg-i- sabj Karanjwa used orally is very beneficial in Amraz-i- Kabid.¹² Powder of Seed Kernel of Karanjwa (1/2 piece) and Laung is used in swelling of Istisqa (Ascites).^8,12 Pod of Karanjwa plant is moistened with water, placed in air and dew overnight and then powdered for use in Yarqan (Jaundice). Amraz A’aza-i-Baul (Disease of Genitourinary) like Hasat Gurda (Renal stone) is treated by using a mixture of Seed Kernel of Karanjwa powder, Honey, and Seer-i-Gao for one week.¹²

Karanjwa plant is used in several ailments of Nizam-i- Tanasuliya (Reproductive system) in both the genders. A Hamul (Suppository) prepared by Seed Kernel of Karanjwa mixed with milk of women is used in cases of infertility.^8,12,16,19 Powder of three roasted Seed Kernel of Karanjwa is used orally in Qeela Mayyih (Hydrocele) for seven days and is also applied locally along with Berg-i-Arand (Ricinus communis).^8,10,12,16 Leaf of Karanjwa is fried in Ricinus seed oil to apply externally on testes in Orchitis.^8,15 Moreover, powder of Seed Kernel of Karanjwa tinctured overleaf of Arand is used to apply on testes.¹⁰ Women with dysmenorrhea revert by using A’ab Berg-i-Karanjwa along with Filfil Shiyah.¹² Oil of Seed Kernel of Karanjwa is also used in Amraz farz (disease of the vagina) like vaginal itching, and Amraz Rahem (disease of Uterus).^8,12,19 In Amraz Jild viz. Phode, Phonsi, Kharish (itching), and Zakhm (Ulcer), massage with oil of Seed Kernel of Karanjwa.^8,19 Powder of Seed Kernel of Karanjwa is also used for itching externally.^8,10,12,17 Seed Kernel of Karanjwa is fried in Rogan-i-Gul or Rogan-i-Til and this oil is externally applied in cases of deep ulcer.^8,10,17 Zumad (Paste) of Karanjwa leaf is applied after heating on Waram (Inflamed part) to resolve it.¹² A’ab Berg-i- Karanjwa is fried in oil to evaporate water content and this oil is used in Kharis (Itching), and deeply infected ulcers.⁹ In an inflamed joint, a paste of Seed Kernel of Karanjwa is externally applied and powder of Seed Kernel of Karanjwa (one piece) is used thrice a day.¹⁵ Powder of Seed Kernel of Karanjwa is also used in Amrz- i-Wabayi (epidemic disease), Zeequn Nafas (Asthma), Juzam (Leprosy), and Eye Tonic.^8,12,19

Properties of Karanjwa

Taxonomy of Plant

Taxonomically, Karanjwa is classified into the following taxonomic categories viz. Kingdom - Planate; Phylum - Magnoliophyta; Division - Magnoliopsida; Class - Angiospermae; Order - Fabales; Family - Fabaceae/ Caesalpiniaceae; Genus - Caesalpinia; Species – bonducella.²⁰

Synonyms

The scientific name of the Karanjwa plant has different synonyms viz. Caesalpinia bonducella (L.) Fleming, Caesalpinia bonduc (L.) Roxb, and Caesalpinia crista Linn.³

Vernacular Name

Karanjwa plants are found in different regions of the world and are known with regional and vernacular names such as Arabi- Aktmakt; Bengaly- Nata, karanj, dehra; English- Fever nut, nicker nut, bonduc nut; French- Bois; Hindi- Kantkarej, Sagar Gota, Kantikaranja; Gujarati-Kakcha, gajega, Kakcha, kachhi; Kannada- Gajjiga, Gajikekayi, Kiri gejjuga; Konkani- Gajago; Marathi-Gajaga, kanchaki, Sagargota; Malayalam- Ban-karetti, Kazhanji, Kaka-moullou; Persian- Khayahe-i-iblees; Sanskrit- Kakachika, Kantakini, Kantakikaranja; Tamil- Kalarciver, Kalarcipparuppu, Kalarcik Koluntu; Telugu- Gaccakayai, Mulluthige; Tulu- Gajige; Urdu- Akitmakit.^{3,8,12,20-22,24}

Mizaj (Temperament)

Different parts of the Karanjwa plant show their specific Mizaj

Hissa mustamela (Part of used)

In USM, the seed kernel is most commonly used for the therapeutic purpose of the Karanjwa plant.^11,12-15,17 Other parts of plants used are viz. root, bark, leaf, and branches.^8,12,17

Taste

Perception of flavor when substances come in contact with the mouth and throat is called taste. The seed kernel of Karanjwa is Talkh (bitter) in taste that is usually perceived in the posterior aspect of the oral cavity.^11,13-15,19

Dosage

Unani scholars used Karanjwa plant in therapeutic dosages to overcome the toxic effect. The seed kernel of Karanjwa is recommended in different doses viz. 0.25^-1 gm,8 0.5^-1 gm,¹³ 1 gm,^14,19 4 Ratti to 2 gm¹⁷ and 2-6 gm.¹⁴ The root bark of this plant is used in a dose of 0.51 gm.¹⁷

Pharmacological actions

There are several pharmacological actions of Karanjwa mentioned in the literature explained by different Unani scholarsviz.Muhallil(Anti-inflammatory),^{5,11,14-16,19} Habis al-Dam (Anti-coagulant),^8,11,16,19 Daf-i-Ta’ffun (Anti- septic),^8,10,13,17 Daf-i-Humma (Anti-pyretic),^{8,10,14,17-19} Anti-malarial,^14,17 Dafe Fasad-i-Balgham (Morbid Phlegmagogue), Dafe Fasad-i-Sauda (Morbid black bile),⁸ Dafe Fasad-i-Dam (Morbid blood),^8,10 Musaffi- i-Khoon (Blood Purifier),^10,13,17 Muqawwi (Tonic),⁸ Kasir Riyah (Carminative),^8,10,16,19 Mudir Hayz (Emmenagogue), Amraz-i-Farz,⁸ Amraz-i-Rahem,^16,19 Muzaffif (Desiccative),^{10,13,14,16,17} Jazib Rutubat,^13-17 Daf- i-Deedan A’ma (wormicidal),^10,17,19 Mullayyin Taba,¹⁰ Daf-i-Tasannuj (Antispasmodic),^10,13,14,17 Waba-i-Amraz (Epidemic disease),^11,16,19 Muqawwi Isnan wa Lissa (Tonic for teeth and Gum),¹⁸ and Mushil Safra.¹²

Therapeutic uses

Karanjwa drug is used in different diseases based on their pharmacological action. Like   -   Humma like Humma Ajamia (Malaria).^8,10-14 Reproductive disorders viz. Uqr (Infertility),^8,12 Qeela-i-Mayya (Hydrocele),^{8,10,13-15,17} Waram Khushiya (Orchitis),^13,15,16 and Iskat-i-Hamal (Abortion).¹² Dermatological diseases viz. Kharis (Itching),^8,10,16,17 Fauda, Phonsi,⁸ Zakhm (Ulcers),^8,10,16 and Juzam (Leprosy).^8,16 Amraz Jigar viz. Istisqa (ascites),^10,13,14,17 and Yarqan (Jaundice).¹² Gastrointestinal diseases viz. Deedan-i-A’ma (Worm infestation), Badhadmi (Indigestion),8,12 Qulinj Reehi (Abodominal pain due to flatulent),10-13,18 Waram- i-lissa (gingivitis),^8,12 Amraz-i-Kabid (Liver Disease),⁵ Bawaseer (Piles),^12,16 Amraz-i-Mida (Gastric disease), Muqawwi Mida (Gastric tonic), and Muqawwi Istiha (Appetizer).¹² Genitourinary diseases viz. Waram-i- Khusiya (Orchitis), Qillat-i-Tams (Amenorrhea),¹¹ Amraz-i-Masana (Disease of urinary bladder),⁸ and Hasat Mathana, and Hasat Kuliya.¹² Neuron Diseases viz. Laqwa (Facial paralysis), Falij (Paralysis),^8,12 and Amraz-i-Barida Dimagiya (Brain disease of coldness).⁹ Respiratory System viz. Zeequn Nafas (Asthma),^8,10,12-15 and Sil (Tuberculosis).¹⁴ Insect Biting viz. Hashrat al- Araz (Insect biting) viz. Scorpion bite.¹² Others viz. Waram (Inflammatory swelling),^5,12,13 Gath (Tumor),⁸ Iltihab Mufasil (Arthritis),^13-16 and Muqawwi Basar (Eye tonic).¹⁹

Naf’akhas (Main function)

Pharmacological action of Advia predominantly occurs after using for therapeutic purposes which is known as Naf ’akhas. Karanjwa plant produces following actions viz. Qulinj Reehi,^10,16,17 Daf-i-Bukhar Kuhna (Chronic fever),^16,19 Nobati Bukhar,¹⁷ and Habis-i-Dam.¹⁹

Badal (Therapeutic interchange)

Advia that can be used in replacement of the main drug is called Badal (substitute). The basis for substitution of drugs for therapeutic purposes are Yaksaniyat-i-Afal (similarity in action), Yaksaniyat-i-Mizaj (similarity in temperament), and Yaksaniyat-i-Zahiri khususiyat (similarity in physical properties/organoleptic characters) of main and substitute drugs.²⁵ The Advia that are substitutes to Karanjwa is Ood-i-Saleeb (Paeonia Officinalis),⁵ Leaf of Karanjwa kernel,^13,17,19 and Gilo (Tinospora cordifolia).¹⁷

Muzir (Adverse Effects)

The adverse effect is an unwanted/unexpected event viz., mild, moderate, or severe that occurs after the therapeutic use of the drug. Therapeutic use of Karanjwa may be produced following adverse effects viz. Increase Yabusat (Dryness),1^{0,13,15-17,19} Toxic for Hot temperament,^16,17,19 Nausea,¹⁷ Lagairy (Weak ^{people),16,19} Chest, and Throat^.14

Musleh (Corrective)

In USM, Musleh is the substance that minimizes or eliminates the adverse effect of a drug. The corrective drugs for Karanjwa plant are Mirch Siyah (Piper nigrum),^{10,13,15-17,19} Dar Fifil (Piper longum),^10,16,17,19 Shah ad (Honey),¹⁶ Tar Ashiya (moist substances),^16,19 Namak (Salt), and Rogan (Oil).¹¹

Advantages of Compound Formulation of Karanjwa

In USM, prevention/elimination of Amraz (disease) is challenged through several Mufrad (Single) and Murakkab (Compound) drugs. Karanjwa compounds have several advantages over their use in singular form like reducing unwanted effects, reducing or enhancing desired effects, changing the unpleasant taste, counteracting toxic properties, and also for synergistic action.⁸

Commonly used formulations of Karanjwa in Unani medicine

There are several compound formulations of Karanjwa used in the management of various ailments by Unani physicians viz. Habb-e-Mubarak, Majoon-e-Gajgah,¹⁶ Habb-e-Karanjwa,^12,13,16 Jawarish Gachgah,^14-16 Ikseer Humma,¹⁴ Habb-e-Rab’a,¹⁴ and Habb-e-Mubarak.¹⁵

Phyto-chemical

Bio-active / Phyto-chemical compounds that possess desirable health benefits are known as Phyto-chemicals. Karanjwa plant has numerous bio-active chemical compounds. The whole plant contains steroidal saponins, hydrocarbons, fatty acids, isoflavones, phytosterols, amino acids and phenolics, alkaloids steroidal saponins, hydrocarbons, fatty acids, isoflavones, phytosterols, amino acids and phenolics, alkaloids present, bonducin (a homoisoflavone); Seed Kernel- Phytosterols- neutral saponins, heptocosane, sitosterol, bitter glycoside, noncrystalline, Bonducin; Seed- Neutral saponins, caesalpin, terpenoids, α- caesalpin, and β-caesalpin; Leave- Pinitol, calcium, glucose, brazzillin; Bark- Homo isoflavonoids, caesalpinianone, and 6-Omethylcaesalpinianone; and Root- Cassane furanoditerpene, bonducellpins (A, B, C, and D), caesalpinin, and diosgenin.^13-17,20-22

Nutritive value of seed kernel

The seed kernel of Karanjwa constitutes several nutrients like Fatty oil (20-24%)- Palmitic, Stearic, Linoceric, linoleic, Oleic, and a mixture of unsaturated acids of low molecular weight; Proteins (7.4-8.4%)- Aspartic acid (9.5%), Lysine (7.9%), Glycine (6.9%), Leucine (6.3%), Histidine (5.1%), Isoleucine (5.1%), Serine (3.8%), r-amino butyric acid (3.7%), Tyrosine (3.7%), Threonin (3.6%), Citrulline (3.6%), Glutamic acid (3.6%), Arginin (3.4%), Proline (3.3-%), L-alanine (2.5%), Methionine (2.1%), Phenyl alanin (1.4%), Valine (1.2%), and Cystine (1.2%); Phyto-chemicals- Phytosterols - neutral saponins, heptocosane noncrystalline, sitosterol, bitter glycoside, and Bonducin; and Carbohydrates- Pentoan (16.8%), Starch (6.1%), water soluble mucilage (4.4%), and 4-o methyl myoinositol hydrate.²²

Reported Pharmacognostical activity

Pharmacognosy is the branch of medical science that deals with the study of crude drugs/ natural states.

Mehra B et al., (2016) conducted a study on the pharmacognostic evaluation of Caesalpinia bonduc (L.) Roxb., and reported that this plant belongs to the Caesalpiniaceae family. The seeds of Karanjwa are greenish-grey to bluish-grey in color, rounded in shape, smooth, shiny, and are about a diameter of 1.2 – 2.5 cm. Seed powder is composed of columnar-palisade cells, parenchymatous cells with resinous contents, bone-shaped thick-walled, roundish to polygonal bearer cells.²⁶

Khandagale PD et al., reported that the seeds of Karanjwa has two parts- epicarp and epidermis. The epicarp is composed of a sclerotic and columnar layer of palisade zone which is wide parenchymatous dainty walled tissue shaping the sacrotesta. Extended vascular strands are seen that spread across the inward seed coat. A preliminary phytochemical study showed the presence of saponins, steroids, alkaloids, flavonoids, and tannins. The previously stated phytochemicals were further confirmed by thin-layer chromatography. This study additionally exhibited physiochemical attributes to distinguish debasement of medications.²⁷

Reported Physicochemical activity

The physicochemical properties of Karanjwa detected in the present study are mentioned in Table 2.²¹

Reported clinical study on Karanjwa

Arora RP et al., (2003) in their study used a tablet Himplasia prepared from Tribulus Terrestris, Asparagus racemosus, Areca catechu, Caesalpinia bonducella, and Crataeva nurvala in Benign prostate Hyperplasia (BPH). They concluded that Himplasia resolved the symptoms of BPH along with control of progressive hyperplasia.²⁸ Gundeti MS et al., (2020) stated that use of AYUSH-64 (3 gm/day) that includes Caesalpinia crista as one of its ingredients in Influenza-like Illness (ILI) is safe and effective.²⁹ Thakar A et al., observed that the use of AYUSH-64 (3 gm/day, orally after food) as an adjuvant in COVID-19 did not produce a significant difference in the main outcomes of COVID-19 as compared to standard care, even though symptomatic inhibition was observed in the AYUSH-64 add-on group as compared to others.³⁰ Reddy RG et al., conducted a study on the asymptomatic and mild form of COVID-19 and concluded that AYUSH-64 (3 gm/day orally after food) as add-on therapy with standard conventional care improved the duration for attaining complete clinical cure and resulted in reduced pro-inflammatory markers in the body.³¹

Reported pharmacological activity of Karanjwa

 Immunomodulatory activity

Shukla S et al., (2009) in their in vivo study concluded that ethanolic extract of Caesalpinia bonducella seed (200–500 mg/kg orally) induced a significant increase in neutrophil adhesion percentage to nylon fibers along with a dose-dependent enhancement in titer value of antibody and raised the delayed-type hypersensitivity produced by sheep red blood cells. It also inhibited myelosuppression in the cyclophosphamide treated rat group and induced positive outcomes towards phagocytosis in the assay of carbon clearance.³² Shruti S et al., (2010) conducted a study on aqueous extract of Caesalpinia bonducella Fleming (400 mg/kg body weight) and observed an increase in mean hemagglutinating antibody (93.03±4) titer and a change in delayed-type hypersensitivity (0.56±0.058 mm) as compared to control.³³

Anti asthmatic activity

Khandagale PD et al., (2019) reported that petroleum extract of ether and ethanol of C. bonducella seeds (50 and 100 mg/kg) exhibited anti-asthmatic activity due to the presence of 2-methyl, 1- hexadecanol.³⁴ Khan HU et al., (2011) observed that crude extract of C. bonducella had antifungal, antibacterial, spasmolytic, and Ca++ channel blocking action.³⁵

Antidiabetic activity

Kannur DM et al., (2006) stated that seed extract of Caesalpinia bonducella (300 mg/kg, orally) has a significant hypoglycaemic effect.³⁶ Parameshwar S et al., (2002) performed a study in which four extracts (ether, petroleum-ether, ethyl-acetate, and aqueous) of the Seed Kernel of Karanjwa were prepared and their hypoglycaemic effect in normal as well as in diabetic rats induced by Alloxan was tested. In normal rats, only ethyl- acetate and aqueous extracts showed a significant blood glucose-lowering effect as compared to glibenclamide. In diabetic rats, ethyl-acetate and aqueous extracts, as well as glibenclamide, produced a significant hypoglycaemic effect, while petroleum ether and ether extracts exhibit a limited hypoglycaemic effect.³⁷ Chakrabarti S et al., (2003) stated that aqueous and ethanolic extracts of Caesalpinia bonducella seeds (250 mg/kg b.w./oral route) produce a significant hypoglycemic effect in the DM type-2 (diabetes mellitus) model.³⁸ Chakrabarti S et al., (2005) in their study observed that both aqueous and ethanolic (80%) extracts of Caesalpinia bonducella (250 mg/kg body weight) produced potent hypoglycaemic activity in the chronic type-2 diabetic model.³⁹ Biswas TK et al., (1997) concluded that aqueous extract of Caesalpinia bonducella (250 mg/kg body weight of rat) produced highly significant hypoglycaemic effect in fed, fasted, glucose loaded, Alloxan and streptozotocin- induced diabetic rat models.⁴⁰ Sharma SR et al., stated that aqueous and 50% ethanolic extracts of Caesalpinia bonducella Fleming (100 mg/kg.) exhibited significant hypoglycemic effects.⁴¹ Bhutkar MA et al., (2018) carried out a study in which extracts of Caesalpinia bonducella seeds and Myristica fragrans were found to possess an antidiabetic effect. Caesalpinia bonducella extract showed significantly higher (p ≤ 0.05) activity than Myristica fragrans.⁴²

Anti-hyperlipidemic activity

Sagar V et al., (2015) concluded in their study that alcoholic extract of Caesalpinia bonducella seeds (200 to 400 mg) significantly increased the levels of total cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, and a significant decrease in high-density lipoprotein were observed in diabetic control rats.⁴³ Sharma SR et al., (1997) conducted a study in which aqueous extracts of Caesalpinia bonducella Fleming (100 mg/kg) produced hypocholesterolemic and hypotriglyceridemic effects in SZ-diabetic rats.⁴¹

Adaptogenic activity

Kannur DM et al., (2006) conducted a study in which Caesalpinia bonducella seed extract (300 mg/kg) has adaptogenic activity using the cold stress model and swim endurance model.⁴⁴

Anthelmintic activity

Jabbar A et al., (2007) concluded that both Caesalpinia crista L. and Chenopodium album L. produced dose and time-dependent effects of anthelmintic activity by causing mortality of worms and reduction of egg hatching.⁴⁵ Wadkar GH et al., stated that extracts of Caesalpinia bonducella L. have significant anthelmintic activity.⁴⁶ Gogoi S et al., (2016) conducted a study in which leaf extract of Caesalpinia bonducella 30 mg/mL caused mortality of Syphacia obvelata in 3.57±0.16 h and Hymenolepis diminuta in 2.5 ± 0.2 h. In a in vivo experiment, the leaf extract showed relatively more  effectiveness on Syphacia obvelata, where its 800 mg/ kg dose exhibited a 93 percent reduction of worm load in mice, as compared to 85 percent worm load reduction of Hymenolepis diminuta in rats.⁴⁷ Karthi J et al., (2011) stated that ethanol, methanol, hexane, and aqueous extracts of Caesalpinia bonducella leaves were effective against helminths viz. Amplostoma caninum and Perionyx excavate.⁴⁸

Antioxidant activity

Sachan NK et al., (2010) reported that chloroform extract of Caesalpinia bonducella seeds produced antioxidant properties.⁴⁹ Shukla S et al., (2009) observed that ethanolic extract of Caesalpinia bonducella could scavenge the superoxide formed by NBT/EDTA system and also inhibited nitric oxide, hydroxyl radical, and superoxide anions. Thus it demonstrated a significant potential for use as a natural antioxidant agent with consequent health benefits.⁵⁰ Gupta M et al., (2004) found that superoxide dismutase levels in the liver of Ehrlich ascites carcinoma bearing mice significantly reduced by 35.6% in comparison with the normal group. Administration of methanol extract of Caesalpinia bonducella leaves in the dose of 50, 100, and 200 mg/kg exhibited levels of superoxide dismutase 9.0%, 19.7%, and 33.2% respectively, compared to the Ehrlich ascites carcinoma control group. The catalase level in the Ehrlich ascites carcinoma control group significantly reduced by 59.1% in comparison with the normal group. Treatment with methanol extract of Caesalpinia bonducella leaves within the dose of 50, 100, and 200 mg/kg increased levels of catalase by 14.8%, 28.7%, and 52.8%, respectively in comparison Ehrlich ascites carcinoma control group.⁵¹ Mobin L et al., (2021) observed that Caesalpinia crista has acceptable antioxidant properties. Phenolic fraction's order of antioxidant activity was by their whole phenolic contents and flavonoid.⁵²

Antidepressant activity

Kumar RS et al., (2006) conducted a study in which methanol extract of Caesalpinia bonducella leaves (100- 200 mg/kg) and Bauhinia racemosa stem bark (100-200 mg/kg) showed a significant decrease in exploratory behavioral pattern and spontaneous activity. It also decreased the activity of muscle relaxation and increased phenobarbitone sodium-induced sleeping time.⁵³

Analgesic, Antipyretic activity, and anti-inflammatory activities

Jagdale RA et al., (2019) concluded that hydroethanolic extract of Caesalpinia bonducella seeds significantly reduced paw volume in acute inflammation, and weight of granuloma formation in chronic inflammation indicating anti-inflammatory activity.⁵⁴ Shukla et al., (2010) in their study concluded that oil of Caesalpinia bonducella seeds (100, 200, and 400 mg/kg, orally) significantly decreased pyrexia and paw volumes, writhes in experimental rats as compared to the control group. These results indicate, antipyretic, anti-inflammatory, and analgesic activity.⁵⁵ Gupta M et al., reported that methanol extract of C. bonducella leaves (50, 100, and 200 mg/kg) produced anti-inflammatory, antipyretic, and analgesic activities.⁵⁶ Shukla S et al., (2015) conducted a study in which ethanolic extract of Caesalpinia bonducella (100, 200, and 400 mg/kg) whole seeds in albino rats demonstrated anti-inflammatory, antipyretic, and analgesic activities.⁵⁷

Anticonvulsive activity

Ali A et al., (2009) observed in their study that petroleum-ether extract of Caesalpinia bonducella (600 and 800 mg/kg) produced a significant anticonvulsant effect due to the presence of phytoconstituents such as proteins, saponins, homoisoflavone, carbohydrates, and sterols.⁵⁸

Antibacterial activity

Mobin et al., (2021) stated that all fractions of Caesalpinia crista (except anthocyanins) and seed coat extract showed considerable antibacterial effects.⁵² Khan HU et al., (2011) concluded that crude extract of Caesalpinia bonducella produced the strongest antibacterial activity which was displayed by the ethyl acetate (80%) and n-butanol (72%) fractions, followed by the crude extract (42% and 46%), against Bacillus subtilis and Escherichia coli respectively.³⁵ Saeed MA et al., observed that four triterpenoids and methanol extract isolated from Caesalpinia bonducella seeds exhibited a wide range of inhibitory activity against both gram- negative and gram-positive bacteria.⁵⁹ Billah MM et al., (2013) found that methanol extract and the other three fractions of the C. bonducella leaves possess a strong antibacterial effect along with moderate cytotoxicities.⁶⁰ Sagar K et al., (2010) expressed that compound, α-(2- hydroxy-2-methyl propyl)-ω-(2-hydroxy-3-methylbut- 2-en-1-yl) polymethylene, collected from ethylacetate leaf extract of Caesalpinia bonducella (L.) Flem. showed antimicrobial activity.⁶¹

Anti-filarial activity

Gaur RL et al., (2008) conducted a study in which crude extracts of Caesalpinia bonducella seed kernel showed macrofilaricidal, microfilaricidal, and female- sterilizing effects against Litomosoides sigmodontis and microfilaricidal and female-sterilizing effects against Brugia malayi in experimental models.⁶²

Anti-diarrhoeal activity

Billah MM et al., (2013) conducted a study in which extracts of Caesalpinia bonducella produced a statistically significant reduction of castor oil-induced diarrhea in a dose-dependent manner. Amongst the four extracts, the ethyl acetate fraction had better activity against diarrhea and produced 51.11 percent inhibition at 400 mg/kg, which was approximately the percent inhibition of the standard drug (57.78%).⁶⁰

Antifungal activity

Shukla S et al., (2011) concluded in a study that ethyl acetate and aqueous extracts of C. bonducella seeds exhibited severe to moderate antifungal effects against the tested fungal species of Candida albicans, Fusarium oxysporum, Aspergillus niger, and Alternaria solani.⁶³ Khan HU et al., (2011) noted that crude extract of Caesalpinia bonducella plant and its fractions produced mild to excellent activity in antifungal bioassays, with maximum antifungal activity against Candida glaberata (80%) and Aspergillus flavus (70%) by the chloroform fractions and n-butanol, followed by the crude extract (70% and 65%).³⁵

Anti-infertility activity

Ahmed RN et al., (2013) stated that ethanolic extract of Caesalpinia bonducella (300 mg/kg/day) showed a significant increase in resorption index, reduction in implantation index, and reduced progesterone levels in experimental albino rats.⁶⁴ Ahmed RN et al., (2012) demonstrated that use of ethanolic extract of Caesalpinia bonducella seed in doses of 100, 200, and 300 mg/kg/day in Groups II, III, and IV, respectively for 10 consecutive days showed a decrease in the hormone levels viz. FSH, LH, progesterone and estradiol, reproductive organ weight and alterations in histoarchitecture of reproductive organs.⁶⁵ Kanerkar UR et al., (2015) administered aqueous extract of seeds of C. bonduc orally for 21 days and showed decreased sperm count in male albino rats. It significantly reduced sperm density and exhibited 9.06%, 25.29%, and 39.79% average increase in anti-spermatogenic activity with 50, 100, and 150 mg/kg, respectively.⁶⁶ Meerwal P et al., (2016) conducted a study in which ethanolic extracts of C. bonducella seeds (200 mg and 400 mg/kg body weight/day) were used for 60 days which showed significantly reduced relative weights of testes and accessory sex glands. It also demonstrated a significant reduction in density, motility, and viability of spermatozoa obtained from cauda epididymis and serum testosterone level in male rats.⁶⁷ Tripathy B et al., (2018) also conducted a study in which a crude ethanolic seed extract of Caesalpinia bonducella (10 doses of 500 mg/kg every alternate day) was used in sexually matured Swiss mice showing a significant decrease (p ≤0.05) in testis weight, and sperm count.⁶⁸ Peerzade N et al., (2009) conducted a study in which use of alcoholic seed extract of Caesalpinia bonducella showed a change in shape and size of the sperm head, midpiece, membrane disruption throughout the length, and distortion of the most anterior region of the head of sperm.⁶⁹

Antitumor activity

Gupta M et al.,(2004) conducted a study in which methanol extract of Caesalpinia bonducella Fleming leaves was used in the dose of 50, 100, and 200 mg/ kg body weight per day for 14 days. After 24 h of tumor inoculation, significant antitumor and antioxidant activity in Ehrlich ascites carcinoma-bearing mice was noted.⁵¹

Antiulcer activity

Patil KS et al., (2010) reported that methanolic extract of Caesalpinia bonducella (Linn.) Flem. leaves (100 and 200 mg/kg) showed a significant reduction in gastric volume, free acidity, total acidity, and ulcer index. It also exhibited significant gastroprotective activity.⁷⁰ Ansari JA et al., (2012) demonstrated that aqueous extract of Caesalpinia bonducella (500, 750, and 1000 mg/kg) produced significant antiulcer and anti-secretary effects.⁷¹

Endocrine function

Salunke KR et al., (2011) conducted a study in which alcohol seed extract of Caesalpinia bonducella showed a significant decrease (p ≤ 0.05) in the duration of the estrous cycle and mean ovarian weight. It also showed no uniform variations in mean uterine weight, serum estradiol, and progesterone levels.⁷² Meera M B et al., (2020) showed that ethanolic seed extract of Caesalpinia bonducella (200 and 400 mg/kg) when used normalized imbalance of luteinizing hormone, prolactin, insulin, testosterone, estrone, and estradiol levels, and decreased follicle-stimulating hormone and progesterone hormone levels Polycystic Ovarian Syndrome induced rats.⁷³ Raveena K et al., (2020) stated that ethanolic seed extract of Caesalpinia bonducella (200-400 mg/kg) significantly decreased tri-iodothyronine (T3) and tetra- iodothyronine, (T4) levels in the presence of tyrosine.⁷⁴

Aphrodisiac activity

Sindete M et al., (2021) conducted a study in which root extract of C. bonduc in male Wistar rats was used and a significantly enhanced sexual behavior viz. intromission frequency, intromission latency, mount latency, and mount frequency was observed.⁷⁵

Hepatoprotective activity

Parthasarathy R et al., (2007) conducted a study in which use of alcoholic extract of Caesalpinia bonducella seeds (300 mg/kg) showed altered levels of the parameters viz. protein, bilirubin, SGOT, SGPT, and ALP were brought back to normal on treatment.⁷⁶ Sarkar R et al., (2012) conducted a study in which they used Caesalpinia crista Linn and found hepatoprotective activity by upregulating antioxidant enzymes and chelating iron to excrete from the body.⁷⁷ Naz F et al., (2021) in an in vivo study used a methanolic extract of Caesalpinia bonduc demonstrating hepatoprotective potential by significantly reducing the hepatoxicity, along with serum enzymes SGPT and SGOT.⁷⁸

Conclusion

Based on the scientific reports, the drug Karanjwa (Caesalpinia bonducella L.) is a potential source in the treatment of several ailments like influenza-like illness, autoimmune diseases, asthma, diabetes, dyslipidemia, anxiety & depression, infertility, Benign prostatic hyperplasia (BPH), hyperthyroidism, microbial & parasitic infection, filariasis, and cancer within its therapeutic dosage. This review advocates further exploration through phytochemical, pharmacognostical, pharmacological, clinical studies to explore other novel applications of this traditionally used drug for the betterment of human health.

Conflict of Interest

None

Acknowledgement

The authors are very grateful for all library staff of the National Institute of Unani Medicine (NIUM), Bangalore, Karnataka, and also awfully gratified to those authors whose study was undertaken in this review manuscript.