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Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

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Open Access Full Text Article                                                              Review Article

Compressive Review on Plant Profile, Phytochemistry and Pharmacology of Crotalaria pallida Action

Mukesh Kumar Patel ¹, Sanjana Soni ²*, Yuvaraj Singh Dangi ³

¹ Sagar Institute of Pharmaceutical Science, Sagar (M.P.) -470002, India

² Sagar Institute of Pharmaceutical Science, Sagar (M.P.) -470002, India

³ Sagar Institute of Pharmaceutical Science, Sagar (M.P.) -470002, India

 

 

INTRODUCTION

The necessity of substituting some medications because of their adverse side effects is a prime example of the widespread use of plants to treat illness and preserve health. Since ancient times, people have used medicinal plants to cure various diseases; this approach is known as phytotherapy ¹. Because medicinal plants include a variety of secondary metabolites, or phytochemicals, that nature can repeatedly manufacture, they have therapeutic benefits. Plants' seeds, bark, roots, leaves, and fruits are the best sources of active metabolites. Consequently, various plants have used these phytochemicals as a defensive mechanism against infections. Since ancient times, phytochemicals have been utilized to cure different illnesses, and they are typically considered safer than synthetic medications ^2,4.

In contrast to synthetic medications, which are seen to be harmful to both humans and the environment, these herbal products are now seen as a sign of safety. Even though herbs have long been valued for their therapeutic, flavorful, and aromatic properties, their significance was temporarily overshadowed by modern synthetic products. However, people are returning to naturals in the hopes of safety and security now that their naïve reliance on synthetics is over. It's time to market them internationally ⁵. For a variety of reasons, traditional medical systems are still frequently used. The use of plant materials as a source of medicines for a wide range of human ailments has gained more attention due to factors such as population growth, an inadequate supply of medications, the exorbitant cost of treatments, side effects from several synthetic drugs, and the emergence of resistance to currently used drugs for infectious diseases ⁵. The plant Crotalaria pallida Aciton, commonly known as “rattle box” in English, is an annual erect herb of about 1.50 m height belonging to the family Fabaceae, which grows gregariously in tropical and sub-tropical regions of India⁶. The stem produces fiber that is comparable to sunn-hemp. Coffee can be replaced with roasted nuts ^6,7. The plant is used as green manure and as a good cover crop in tea, coconut, and rubber plantations in Sri Lanka and Southeast Asia to prevent soil erosion. The plant's various parts are used in traditional medicine to alleviate joint swelling and urinary tract infections ⁷.A novel antimicrobial peptide named Cp-AMP has been isolated and characterized from the seeds of Crotalaria pallida which showed promising bioactivity against urinary disease-causing bacteria Proteus as well as a potent phytopathogenic fungi Fusarium oxysporum ⁸. The leaves showed estrogenic and mutagenic activities ⁹. as well as antibacterial activities ¹⁰. Chemical investigation on this plant is confined to alkaloids and flavonoids only ^11,12.

Crotalaria is one of the largest genera in tropical Africa. The genus includes 690 species that are mainly situated in Africa and Madagascar.  the. Species have also been found throughout in India ². This is an erect shrub, annual short-lived perennial herb of 1.5 m or more tall. Taproot white or brown and stem grooved, solid, glabrous. Leaves trifoliolate, alternate spiral, stalked, leaflets elliptic, more than 2 cm long/ wide, hairy on upper surface, margin entire, apexobt use base acute, pinnately veined. Flowers bisexual, grouped together in a terminal raceme, stalked, petals 5, yellow. Fruit a rounded. This species is used in traditional medicine. The plant is used to treat urinary problems and fever, a poultice of the roots is applied to swelling of joints and fever, and its leaves are used as a vermifuge ^13,14. The plant is grown as a ground cover and a green manure crop, especially in the inter-rows of rubber trees and coconut palms. Flowers are eaten as a vegetable in Cambodia, where the seeds are roasted and grounded for use as a sort of coffee beverage. The roots are sometimes chewed with betel nuts in Vietnam. In traditional medicine, the plant is used to treat urinary problems and fever, a poultice of the roots is applied to swelling of joints and an extract of the leaves is taken to expel intestinal worms ¹⁵. India is home to over 81 species of Crotalaria, with Crotalaria pallida Aiton being one of the more noteworthy ones ¹⁶. Most Crotalaria species are used as medicinal agents in India to treat various illnesses ¹⁷. The phytochemical constituents are also reported in Crotalaria pallida Aiton include: 

Alkaloids, Flavonoids, Phenols, Carbohydrates, Proteins, Steroids, Tannins, Saponins, Gums, and Reducing sugars. Synonymsare Crotalaria mucronata Desc, Crotalaria striata DC, Crotalaria falcata VAHL ex DC, Crotalaria brownei DC., Crotalaria fertilisDelile, Crotalaria hookeri Arn., Crotalaria pisiformis Guill. &Perr., Crotalaria siamica F.N. Williams, Crotalaria striata var. acutifolia Trin., Crotalaria tinctoriaBaill, Crotalaria zuccarininana D. Dietr ^18,20.

 

 

            

Figure 1: Flower⁵¹                 Figure 2: Leaf⁵¹                                                                                            Figure 3: Fruits⁵¹

 

 

RESEARCH METHODLOGY

A review of scientific literature from a variety of sources, including Google Scholar, Web of Science, SciFinder, Scopus, Science Direct, PubMed, Scielo, Springerlink, Google Patents, Espacenet, BioMed Central (BMC), and Medline, was conducted in order to identify relevant information on the botany, medicinal uses, phytochemistry, and biological activities of C. pallida. Common English names, dissimilar scientific names and synonyms, biological activities, medicinal uses, ethnobotany, ethnopharmacology, medicinal, pharmacology, phytochemistry, and therapeutic value, C. pallida, black oil plant, oriental bittersweet, climbing staff tree, Jyotishmati, and intellect tree were among the keywords used to identify pertinent data. Books, book chapters, theses, websites, and conference proceedings were the sources of further literature

OCCURENCE AND DISTRIBUTION

The native range of Crotalaria pallida Aiton is the tropical and subtropical Old World, including Africa, the Indian subcontinent, and Asia. It is commonly found in India, Sri Lanka, and throughout South-East Asia. However, due to widespread cultivation, its natural distribution is obscured. It has escaped and is now naturalized in many other regions, including: The Lucayan Archipelago, The entire Caribbean region, Mexico south to South America, The Pacific, and Australia. Crotalaria pallida Aiton is an annual, perennial, or subshrub that grows primarily in the seasonally dry tropical biome. It is commonly found in waste lands and roadsides. Crotalaria pallida is NOT native to the Lucayan Archipelago. It is native to Africa, the Indian subcontinent, and Asia. It has escaped and is now naturalizing in the Lucayan Archipelago, the entire Caribbean region, and Mexico south to South America, the Pacific, and Australia. Africa Tanzania, Uganda, Northeast Tropical Africa Chad, Ethiopia, Sudan, South Tropical Africa Angola, Malawi, Mozambique, Zambia, Zimbabwe Southern Africa KwaZulu-Natal, Northern Provinces, Swaziland, West Tropical Africa Benin, Burkina, Gambia, The Ghana, Guinea, Guinea-Bissau, Ivory Coast Liberia, Mali, Niger, Nigeria, Senegal, Sierra Leone, Togo, West-Central Tropical Africa Burundi, Cameroon, Central African Republic, Congo, Equatorial Guinea, Gabon, Gulf of Guinea Is, Rwanda, Zaire, Western Indian Ocean Comoros, Madagascar, Asia-Temperate China China North-Central China South-Central, China Southeast, Hainan Eastern Asia Taiwan, Asia-Tropical Indian Subcontinent Assam, Bangladesh, East Himalaya, India, Nepal, Pakistan, Sri Lanka, West Himalaya^21.

BOTNICAL DESCRIPTION

Crotalaria pallida, commonly known as the smooth crotalaria, is a species of flowering plant within the family Fabaceae

Stem- usually flowers and fruits as a shrub 1-1.5m tail but also flowers as an herb 

Leaves- Compound leaf petiole about -1-6 cm long. Middle leaflet larger than the lateral leaflets. Leaflet blades about 1.5-8x0.6-4cm, broadest at or above the middle.   Leaflet stalks about 0.3cmlong. Stipules about1-3mm long, recurved, hairy when young, purple at the base but green at the apex.

Flowers -Inflorescences about 15-45 cm long. Flowers borne singly in the axils of deciduous, about 2-5mm long, bracts. Calyx is about 6- 7.5 mm long, and the lobes are about as long as the tube. Petals: standard about 10- 12x8 mm; wings much shorter than the keel; keel about 12- 15 mm long. Standard and keel marked by red-purple striations (veins). Stamens 10, dimorphic, five anthers long and basifixed, and five anthers short and dorsifixed. Another filament fused to form a tube open on one side. Pollen orange. Ovary densely clothed in white hairs.

Fruit – Pods cylindrical, about 30-45x8-9mm, grooved on one side, clothed in erect hairs. Seeds rattle when pods are shaken. Seeds about 3x2mm, mottled light and dark brown, laterally compressed, +/- hook-shaped or boomerang-shaped. Radicle beside and +/- parallel to the axis of the cotyledons.

Seedlings-Cotyledons about 13-17x6-7mm. First pair of leaves trifoliolate and alternate. At the tenth leaf stage: stipules filiform to narrowly triangular, about1-5mm long. Stems, terminal buds and petioles densely clothed in pale brown prostrate hairs. Two small ridges run down the stem from the base of each petiole. Seed germination time 6 to 25 days.

This shrub (annual or short-lived perennial herb) has height of about 1.5 m. The stout stem is hairy and has longitudinal grooves. Leaves are trifoliate with a 2– 8.5 cm long petiole, leaflets 3-13 x 2–5 cm and elliptical to obovate. Flowers are yellow, often reddish brown veined and borne on 15–40 cm long racemes, each with 20-30 flowers. Fruits are 3-5 x 0.6-0.8 cm, 30-40 seeded that are heart-shaped, 3 x 2 mm, shiny, mottled ochre and dark grey-green or brown ²².

The plant is grown as a ground cover and a green manure crop, especially in the inter-rows of rubber trees and coconut palms. Flowers are eaten as a vegetable in Cambodia, where the seeds are roasted and grounded for use as a sort of coffee beverage ²².

PHYTOCHEMICAL CONSTITUENTS

Several classes of phytochemicals, including pterocarpanoids, alkanes, alkaloids, flavonoids, terpenes, and fatty acids, have been shown to be present in C. pallida. Below is a discussion of each of these classes: 

1 Pterocarpanoids

Major pterocarpanoids namely, crotafurans A (5ʹ-(1-Methylethenyl)furo[2ʹ,3ʹ: 9,10]pterocarpan-3-ol=rel-(5bR,11bR)-5b,11b-Dihydro-2- (1-methylethenyl)-6H-furo[2ʹ,3ʹ: 6,7]benzofuro[3,2-c][1]benzopyran-9-ol); crotafurans B (1-(3-Hydroxyfuro[2ʹ,3ʹ: 9,10] pterocarpan-5ʹyl)ethanone=rel-1-[(5bR,11bR)-5b,11b-Dihydro-9-hydroxy-6H-furo[2ʹ,3ʹ:6,7]benzofuro[3,2-c][1]benzopyran-2-yl]ethanone); crotafurans C (5ʹ-(1-Methylethenyl)furo[2ʹ,3ʹ: 9,10]pterocarpan-3,6adiol= rel-(5bR,11bR)-5b,11b-Dihydro-2-(1-methylethenyl)-6H-furo[2ʹ,3ʹ: 6,7]benzofuro[3,2c][1]benzopyran-5b,9-diol); crotafurans D (1-(3,6a-Dihydroxyfuro[2ʹ,3ʹ: 9,10]pterocarpan-5ʹ-yl)ethanone rel-1-[(5bR,11bR)-5b,11b-Dihydro-5b,9-dihydroxy-6H-furo[2ʹ,3ʹ:6,7] benzofuro[3,2-c][1]benzopyran-2yl]ethanone), and Crotafurans E (5ʹ-(1-Methyl-1,2-dihydroxyethyl)-furo [2ʹ,3ʹ:9ʹ10]pterocarpan-3-ol) have been reported from the bark of C. pallida ²³.

2 Alkane   

Thin-layer chromatography (TLC) and Gas liquid chromatography (GLC) studies characterize the n-alkane composition in C. pallida epicuticular wax of leaves, flowers and seeds and identified twenty-one n- alkanes from C₁₅ to C₃₅. In the leaf wax long chain hydrocarbons, Heneicosane (C₁₉), Tricosane (C₂₃), Tertacosane (C₂₄), Pentacosane (C₂₅), Hexacosane (C₂₆), Heptacosane (C₂₇), Octacosane (C₂₈) Nonacosane (C₂₉) and Hentriacontane (C₃₁) were predominant whereas flowers and seeds exhibited higher values of medium-chained n-alkanes (C₁₇-C₂₇) ²⁴.

3 Fatty acids 

Gas chromatography- Mass spectrometry (GC-MS) analysis of C. pallida oil revealed the presence of unsaturated fatty acid in greater amount than saturated fatty acids. Arachidic acid (37.99%) and palmitic acid (32.48%) are the most abundant saturated fatty acids whereas in linolaidic acid (10.47%) is reported to be predominant unsaturated fatty acid ²⁵. 

4 Flavonoids 

isolated a new isoflavones 5,7,4ʹ-trihydroxy-2ʹ-methoxyisoflavone along with some other constituents namely b-sitosterol, lupeol, morin, weighteone, 2ʹ-hydroxygenistein, daidzein and 2ʹ-hydroxydaidzein, taxifolin, naringenin, quercetin-7-O-b-d-glucopyran-oside, and naringenin-7-O-b-dglucopyranoside from the barks of C. pallida.²⁶. Three new flavonoids viz. cropalliflavones A, cropalliflavones B and cropalli-flavones C and two homoisoflavonoids along with six previously known flavonoids diosmetin, luteolin, acacetin-8-C-neohesperidoside, obovatachalone, 5,3ʹ,4ʹ-trihydroxy-2ʹʹ,2ʹʹdimethylpyrano(5ʹʹ,6ʹʹ:7,8) isoflavone and alpinumisoflavone, have been isolated from the seeds of C. pallida ²⁷.

5 Alkaloids 

 Two more alkaloids, cropallin A, cropallin B have also been reported from C. pallida seeds ²⁷ Usaramine-N-oxide and usaramine alkaloids isolated from the seeds of C. pallida using High Pressure liquid chromatography-Mass spectrometry (HPLC-MS) ²⁸.

6 Miscellaneous compounds 

Spectroscopic analysis of C. pallida  seeds showed one sesquiterpenoids, (-)-methyldihydrophosphate, six phenylpropanoids namely, ferulic acid, p-hydroxyl ethyl cinnamate, ethyl caffeate, phydroxycinnamic acid methyl ester, 4,4ʹ-bis(1-propenoic acid methyl ester)-3ʹ-methoxydiphenyl ether, and ethyl (E)-3-(4-(4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-2-methoxyphenoxy) phenyl) acrylate; one phenolic acid, sonchifolinin B; and one lignin, ethyl (E)-3-[(2R,3R)-2,3-dihydro-2-(4-hydroxy-3-methoxyphenyl)- 7methoxy-3-ethoxy carbonyl-1-benzofuran-5yl] propenoate ²⁷.

MEDICINAL AND TRADITIONAL USES

The plant is used as green manure, young seeds are used as food, roasted ripe seeds can be substituted for coffee, stem fiber is used as a material for thread, etc. C. pallida is used as a ground cover and a green manure crop throughout the humid tropics, through on a limited scale. In tea, rubber, and coconut plantations in Sri Lanka and Southeast Asia, and in cocoa plantations in West Africa, it is used as a green manure and planted in the interrows to reduce erosion. It is one of the oldest green manure crops in Indonesia, but lost popularity because of its susceptibility to diseases and pests ^29,31.

Up to the 1960s, C. pallida was widely cultivated for soil cleansing and as a green manure crop in the south-earth United States, replacing the more toxic Crotalaria spectabilis Roth. It's useful as a fodder crop as well. However, because the seed can occasionally become poisoned when blended with fodder grains, its usage is no longer advised. The seeds were once used to make a fermented food in west Java. To get rid of the toxic parts, the seeds were cooked for two hours, wrapped in banana leaves, and allowed to ferment for a few days. The blooms are used as a vegetable in Cambodia. In Indochina, roasted seeds are used to make a type of coffee. The roots are occasionally consumed with betel nut in Vietnam.

In traditional medicine, C. pallida is used to treat urinary problems. A poultice made of the roots is applied to painful swelling of joints, and an extract of the leaves is taken as a vermifuge. In Laos the plant is used to reduce fever ^29,31.

CULTIVATION

A plant of the lowland tropics and subtropics.

Elevation- it has been successfully grown at elevations up to 1,800 miters ³².

Rainfall- It grows in a wide range of annual rainfall conditions, from 850 mm to over 3,000 mm, and occurs occasionally in rather dry locations.

Temperature- The average annual temperature varies from 16-26°c Succeeds on a wide range of soils, except on peat soils that developed under coarse grass. It is considered well suited to sandy soils and has succeeded in saline conditions in Thailand. It requires a sunny position, growing poorly in shade. Often grown as a green manure, the plant can escape from cultivation and become naturalized. It is reported to be invasive in many areas, where it grows in open and disturbed sites such as pastures, waste ground, roadsides and sand dunes at elevations up to 1,070 miters.

This species has a symbiotic relationship with certain soil bacteria, these bacteria form nodules on the roots and fix atmospheric nitrogen. Some of this nitrogen is utilized by the growing plant but some can also be used by other plants growing nearby.

It is cultivated by seed and the seedling will emerge after 21-30 days after sowing. The germination rate of fresh seeds is higher compared to the stored ones. The 30 cm tall-plants must be topped in order to promote branching ^32,34.

REPORTED PHARMACOLOGICAL ACTIVITY 

Here, the several significant pharmacological actions of C. pallida are examined.

1. Antioxidant Activity 

Alam et al., 2014evalutedAntioxidant properties of C. pallida were investigated by various workers using Ferric ion reducing antioxidant power (FRAP), 2,2-diphenly-l-picrylhydrzyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline6-sulfonic acid (ABTS). The leaves extract exhibited free radical scavenging activity with IC₅₀ value of 37.60µg/ml compared to standard ascorbic acid IC₅₀ value of 16.95µg/ml ³⁵.

Govindappa et al., 2011a studied Five different extracts namely ethanol, ethyl acetate, chloroform, petroleum ether, and aqueous extract of C. pallida were used to screen antioxidant activity. The ethanol, ethyl acetate and petroleum ether extract exhibited greater scavenging activity in both DPPH and FRAP assays. The FRAP and DPPH activity of the extracts was 88%, 72% and 73% and 3617.89±0.03, 2189.33±0.01 and 1133.26±0.03, respectively ³⁶.

Kiruthiga et al., 2014 investigated The enzymatic superoxide dismutase (SOD) antioxidant assay of in vivo leaves and in vitro callus of C. pallida showed high activity of 0.78±0.036 units/g and 3.563±0.16 units/g of tissue, respectively.  The DPPH, hydroxyl scavenging activity (HRSA) and superoxide anion radical scavenging activity of in vivo leaves extract and in vitro callus tissue showed the IC₅₀ values of 25±0.16 and 23.57±0.07, 90.18±3.57 and 77.41±2.5, 72.58±1.55 and 42.96±0.29, respectively ³⁷.

Islam et al., 2018 examined the Petroleum ether extract of C. pallida stem exhibited remarkable DPPH free radical scavenging activity with IC₅₀ value of 126.96µg/ml. Petroleum ether, chloroform and methanol stem extract of C pallida were most effective in scavenging free radical³⁸.

2. Antibacterial activity 

Alam et al., 2014Disk diffusion method was performed to screen for antibacterial activity of different solvent extracts such as ethanol, ethyl acetate, chloroform, petroleum ether and aqueous extracts of C. pallida. The ethanol leaves extract exhibited mild antibacterial activity against Vibrio cholera, Shigella dysenteriae and Shigella flexneri compared to standard drug kanamycin³⁵.

Islam et al. (2018 studied The Petroleum ether and chloroform stem extract, which showed mild to moderate antibacterial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, except Bacillus cereus, while the methanol extract did not show any inhibitory effect against the tested bacteria ³⁸.

Pelegrinietal et al., 2009 reported A novel peptide Cp-AMP with molecular mass 5340Da was isolated from the seeds of C. pallida. The Cp-AMP inhibits the development of Fusarium oxysporum and Proteus sp. a gram-negative bacteria ³⁹.

Govindappa et al., 2011a evaluated Ethanol extract showed the maximum inhibition against bacteria and fungi. The minimum microbial concentration (MMC) of ethanol, petroleum ether and ethyl acetate extracts ranged from 0.3-3.2mg/ml for bacteria and 0.6-4.0mg/ml for fungi respectively ³⁶.

Ukil et al., 2016 said The fatty acid of C. pallida leaf showed antibacterial activity against Bacillus subtilis, Acinetobacter junii and Escherichia coli with MIC value of 80 ± 0.58, 10 ± 0.25 and 10 ± 0.14 respectively ⁴⁰.

3. Anti-inflammatory activity 

Bulbul et al., 2017 evaluated anti-inflammatory activity by the carrageenan-induced paw oedema test in rats. At both 50 and 100mg/kg doses the carrageenan induced rat paw oedema was greatly reduced ⁴¹.

Hu et al., 2017 said Cropalliflavone C isolated from C. pallida seeds showed moderate anti-inflammatory activity with IC₅₀ value of 16.07µM. The Cropalliflavone A, Cropalliflavone B, Usaramine-N-oxide, Cropallin A and Cropallin B exhibited weak activity with IC₅₀ value ranging from 45.44 to 78.50 µM while luteolin, usaramine and acacetin-8-C-neohesperidoside were ineffective ²⁷.

Weng et al., 2003 reported Thepterocarpanoids, crotafurans A and B isolated from C. pallida inhibited the NO₂^- accumulation in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage-like cells with IC₅₀ value of 23.0±1.0 and 19.0±0.2µM, respectively ²³.

4. Anthelmintic activity

Panda et al (2015a) used ethanol, ethyl acetate, n-butanol and petroleum ether extract of leaves of C. pallida to evaluate anthelmintic activity on Indian earthworms Pheretimaposthuma. Among all the extracts, petroleum ether and ethanol exhibited significant and dose-dependent anthelmintic activity. Compared to standard drug albendazole petroleum ether showed better activity ⁴².

Alam et al., 2014 used The ethanol leaves extract of C. pallida showed dose-dependent decrease in paralysis and death time of Paramphistomumcervicompared to reference drug albendazole ³⁵. 

5. Cytotoxic and Apoptotic activity 

Hu et al., 2017 examined Flavonoids and alkaloids from the seeds of C. pallida were used to evaluate cytotoxicity against the MCF-7 and CaCo₂ cell lines. Cropalli flavone B showed moderate cytotoxicity against MCF-7 cell line with IC₅₀ of 6.77µM while other compounds showed little or no cytotoxicity against MCF-7 and CaCo₂ cell lines.²⁷.

Dinakar and Govindappa, 2017 studied Low molecular weight proteins (LMWPs) with a molecular weight of against Allium cepa root tips and MCF-7 cell lines respectively. The 14KDa protein exhibited antimitotic properties and apoptotic activity and can be used to prevent the progression of cancer in susceptible individuals ⁴³.

Umashanakr et al., 2015 evaluted The compound, coumarin isolated from the endophyte of C. pallida when tested against HeLa cancer cell lines. Coumarin significantly inhibited the proliferation of HeLa cell lines with an IC₅₀ value of 0.156µg/ml ⁴⁴.

6 Anti-HIV properties 

Govindappa et al. (2013 investigated Coumarins isolated from the flowers, stems, roots, and leaves of C. pallida by the microwave extraction method. The flower extract having coumarins greatly inhibited the HIV replicating enzymes such as βglucosidase, α-glucuronidase, α-glucosidase, pepsin, reverse transcriptase and protease. The C. pallida coumarins can be a potential drug to control HIV disease ⁴⁵.

Govindappa et al., 2011b examined HIV protease inhibitor activity was determined by pepsin assay using methanol and ethanol extract of different parts (leaf, stem, and flower) of C. pallida. The methanol and ethanol extracts of flower and stem exhibited significant inhibition of pepsin enzyme as compared to standard Pepstatin A ⁴⁶.

7. Antidiabetic activity 

Panda et al., 2015b used The ethanol, n-butanol, ethyl acetate and petroleum ether extracts of C. pallida leaves were used to determine the antidiabetic activity in alloxan-induced diabetic rats. The extract at 300mg/kg body weight exhibited greater antidiabetic activity on the first, third, fifth and seventh days. The ethanol extract showed highly significant antidiabetic activity while other extracts displayed mild effect compared to standard drug Glibenclamine. The ethanol leaves extract of C. pallida can be a potential antidiabetic drug ⁴⁷.

8. Analgesic and antipyretic activity 

Panda et al., 2015c said Substances that reduce pain sensation are called analgesics. The C. pallida is used extensively by tribal people for treatment of various diseases. Analgesic and antipyretic activity were evaluated on albino mice by hot plate and tail immersion methods and Brewer’s yeast-induced pyrexia, respectively. The ethanol, n-butanol, ethyl acetate, and petroleum ether extracts of C. pallida were used at 100 and 200mg/kg to determine analgesic and antipyretic activity. The ethyl acetate and n-butanol exhibited greater analgesic effect at 200mg/kg than the other two extracts compared to standard pentazocine (10mg/kg). On the other hand, petroleum ether and ethanol leaves extract at 200mg/kg showed significant antipyretic activity compared to standard drug paracetamol (100mg/kg) ⁴⁸.

9. Anti-proliferative activity 

Rumondor et al., 2017 evaluated the the Anti-proliferative activity of C. pallida leaves and seeds extracts by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 breast cancer cell lines. Four different extracts (ethanol, ethyl acetate, n-hexane and aqueous) were used. The ethyl acetate extract exhibited significant anti-proliferative activity with IC₅₀ value of 29.67µg/ml. The ethyl acetate extract of C. pallida can be a potential anti-cancer drug ⁴⁹.

10. Miscellaneous activity 

Bulbul et al., 2017 reported Anti-nociceptive activity was evaluated using acetic acid-induced writhing test, formalin-induced paw licking teat and tail immersion methods in mice. Acetic acid-induced test at 50mg/kg and 100mg/kg significantly reduced the pain by 37.50% and 47.70% respectively. The ethanol leaves extract of C. pallida greatly inhibited formalin-induced paw licking in mice. The extract at 100mg/kg and produced 40.44% and 27.94% inhibition in the first phase and 50mg/kg body weight produced 48.15%, and 20.37% inhibition in second phase. In the tail immersion test, the ethanol extract caused significant inhibition of pain 64.91% at a dose of 100 mg/kg  ⁴¹.

Kabir et al., 2015 examined In vitro thrombolytic activity of methanol extract of C. pallida exhibited clot lysis effect with 41.81±4.12% compared with standard streptokinase 75±0.09% while sterile distilled water showed negligible clot lysis with 4.8±0.12%. ⁵⁰.

Acknowledgements: The Sagar Institute of Pharmaceutical Science, Sagar (M.P.) -470002, India, provided the required research facility, for which the authors are thankful.

Author contribution: Research Methodology: Mr. Mukeh Kumar Patel

Pharmacological activity and phytochemical constituents: Sanjana Soni

Occurrence, Distribution and Botanical description:  Dr. Yuvaraj Singh Dangi

Funding source: The authors declared that this research has received no financial support.

Conflicts of interest: All authors state that they have no conflicting interests concerning this work.

Ethical approval: This research does not involve experiments on animals or human subjects.

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