Department of Pharmacognosy & Herbal Medicine

CRYPTOLEPIS SANGUINOLENTA           

TAXONOMY

Family: Apocynaceae     Order: Gentianales    Genus: Cryptolepis     Species:  C. sanguinolenta

Local name

 Nibima(Twi), Kadze(Ewe), Gangnamau(hausa), Nurubima( Guans).

BOTANICAL DESCRIPTION

Cryptolepis sanguinolenta is a slender, scrambling shrub native to Africa, characterized by its twining stems and opposite, simple leaves that can grow up to 7 cm long and 3 cm wide. The plant exudes a yellowish latex that turns red when exposed, and it features few-flowered cymes with greenish-yellow flowers that are bisexual and regular, measuring about 1.5 cm long. The fruits are horn-like, paired in linear follicles, containing tiny, pinkish seeds encased in silky hairs. The roots, which can range from 0.4 to 6.6 cm in length, have a bitter flavor and a yellowish-brown color with longitudinal ridges when dried. This plant is traditionally used in West Africa for treating various ailments, including malaria and respiratory conditions.

ETHNOBOTANICAL USES

The plant is used in the treatment of malaria, diarrhea, and respiratory conditions.

PHYTOCHEMICAL COMPOSITION

Cryptoquindoline, cryptoheptine, biscryptolepine, 11-hydroxycryptolepine, quindolinone, isocryptolepine (Cryptosanguinolentine), neocryptolepine, quindoline, cryptolepine  and cryptospirolepines are among the structurally similar alkaloids identified in the plant. Many indoloquinoline alkaloids, such as cryptolepine, hydroxycryptolepine, and cryptolepinone, are found in the roots of the Cryptolepis sanguinolenta. Also, the ethanolic root extract yielded two new indoloquinoline alkaloid glycosides, called Cryptospirosanguine A (1) and B (2). This plant also yielded the first isolation of two known terpenoids.

CHEMICAL STRUCTURE

PHARMACOLOGICAL PROPERTIES

ANTITHROMBOTIC

Studies showed that Cryptolepis sanguinolenta has a strong antithrombotic property. In a mouse model, it offered 25% maximum protection at 1 mg/kg, but dipyridamole only had a 20% impact at 2 mg/kg. Lower dosages of cryptolepine were less effective. Aspirin and indomethacin both showed dose-dependent, increased levels of protection. Dipyridamole and cryptolepine together proved to be more beneficial than either medication alone. Interestingly, a 20% ethanol vehicle on its own offered 45% protection and improved the antithrombotic effects of all tested medications. This also indicates that it has a vasodilatory effect.

ANTI ADRENERGIC ACTIVITY

The alkaloid cryptolepine of Cryptolepis sanguinolenta demonstrates dual adrenergic actions. It acts as a powerful antagonist on the rat vas deferens while also increasing the contractile effects of modest doses of noradrenaline. Cocaine prevents this potentiation, indicating that noradrenaline absorption by neurons is inhibited in the process. With its distinct profile of antagonistic and potentiating adrenergic actions, Cryptolepis sanguinolenta is a potentially medicinal plant with intriguing pharmacological properties.

 

 

ANXIOGENIC ACTIVITY

Studies  found that Cryptolepis sanguinolenta aqueous extract exhibits an anxiogenic-like effect in mice, characterized by increased anxiety-related behaviors, contrary to its traditional use as a sedative for insomnia.

ANTI-ASTHMA ACTIVITY

Studies  revealed that Cryptolepis sanguinolenta aqueous extract exhibits strong anti-asthmatic properties in both the early and late stages of the condition. During the first 24 hours, guinea pigs' histamine-induced bronchoconstriction was considerably and dose-dependently reduced by cryptolepine. It stabilized the mast cells against degranulation and decreased the release of bronchial mucus. Similar to the common medication dexamethasone, cryptolepine reduced ovalbumin-induced airway obstruction, inflammation, and remodeling in the late phase. In animals that were already sensitized, cryptolepine also reduced allergen-induced hypersensitivity. These results offer scientific support for the long-standing usage of extracts from Cryptolepis plants to treat respiratory conditions including asthma.

ANTI-HYPERGLYCEMIC ACTIVITY

Cryptolepis sanguinolenta exhibited antihyperglycemic properties, and researchers have synthesized various analogues to evaluate their efficacy in vitro and in a mouse model of non-insulin-dependent diabetes mellitus. When administered orally to a mouse model of diabetes, the indoloquinolone alkaloid cryptolepine, which was isolated from Cryptolepis sanguinolenta, dramatically decreases glucose. Due to cryptolepine's antihyperglycemic action, plasma insulin concentration significantly drops, and there is evidence that insulin-mediated glucose disposal is improved. Furthermore, 3T3-L1 cells' absorption of glucose is enhanced by cryptolepine.

ANTIMICROBIAL ACTIVITY

Cryptolepine showed significant anti-staphylococcal action against S. aureus NCTC 10788, with a MIC of 5 μg/ml, and lytic impact, indicating its antibacterial activities. Cryptolepis sanguinolenta root completely cleared pan-sensitive H37Rv and rifampicin-resistant TMC-331 Mycobacterium tuberculosis strains at 50 mg/ml and 25 mg/ml, respectively, with MIC values of 1.17 mg/ml and 1.56 mg/ml. Aspergillus niger and Candida albicans were among the bacteria that the methanolic extract of Cryptolepis sanguinolesnta leaves showed antimicrobial activity against. These bacteria included Salmonella typhii, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Bacillus subtilis. For each of the studied bacteria, the minimum inhibitory concentrations (MICs) varied from 6.25 mg/mL to 12.5 mg/mL.

ANTIMALARIAL ACTIVITY

Cryptolepine, an alkaloid from Cryptolepis sanguinolenta, has been shown to have potential antimalarial effects, including decreased parasitemia in animal models and strong inhibitory effects against chloroquine-resistant Plasmodium falciparum strains. The antimalarial medication artesunate (Art) was less effective against Plasmodium berghei infection in rats when combined with C. sanguinolenta extract. P. berghei was not as well-suppressed in rats treated with Cryptolepis sanguinolenta (Cryp) for two weeks and administered the Cryp/Art combination due to their greater levels of parasitemia. Extracted cryptolepine from 9–12-month-old regarding Plasmodium falciparum Dd2, Cryptolepis sanguinolenta plants showed the highest drug selectivity index (2.15–3.91) and anti-plasmodial activity (IC50 = 2.56–4.65 μg/mL), indicating that they may be used to treat malaria.

ANTI-HYPERLIPIDEMIC ACTIVITY

The crude ethanolic extract of Cryptolepis sanguinolenta possesses antihyperlipidemic qualities, and in HepG2 cells, isocryptolepine has been shown to have high pro-low-density lipoprotein (LDL) absorption. This indicates that since lowering LDL cholesterol is essential for the development of atherosclerotic cardiovascular disease, isocryptolepine may be a promising lead molecule for the creation of innovative antihyperlipidemic medications.

ANTIOXIDANTS ACTIVITY

The ethanolic extract of Cryptolepis sanguinolenta showed a greater total phenolic content, suggesting possible antioxidant qualities. Strong antioxidant-producing Cryptolepis sanguinolenta inhibits xanthine oxidase and superoxide scavengers, hence lowering the generation of superoxide radicals, a primary cause of oxidative stress and a potential natural remedy for illness prevention.

ANTI-INFLAMMATORY ACTIVITY

Studies revealed that Cryptolepis sanguinolenta exhibited anti-neuroinflammatory characteristics of (CSF) which include suppressing pro-inflammatory mediators in glioblastoma cells and macrophages, modulating transcription factors and inflammatory cytokines, and shielding glioblastoma cells from LPS-induced cytotoxicity. According to these results, C. sanguinolenta polysaccharides may be used to treat or prevent neurodegenerative illnesses that are associated with neuroinflammation.

ANTI-CANCER ACTIVITY

Extracted cryptolepine from 9–12-month-old Studies on Jurkat leukemia cell lines revealed that Cryptolepis sanguinolenta plants are cytotoxic, suggesting that cryptolepine may be used to treat cancer.

ANTI-PARASITE ACTIVITY

In vitro, Cryptolepis sanguinolenta showed strong inhibitory action against Babesia duncani. With an IC50 of 3.4 μM, the active component cryptolepine from Cryptolepis sanguinolenta demonstrated activity that was either on par with or less than that of quinine and clindamycin, two commonly used medications. Moreover, B. duncani treated with cryptolepine at IC50 values of 1×, 2×, 4×, and 8× was unable to develop in subculture.

ANTI-DIABETIC ACTIVITY

The ethanolic extract of Cryptolepis sanguinolenta dramatically lowers plasma glucose, total cholesterol, triglycerides, and LDL cholesterol levels via inhibiting glucose transport and absorption. Additionally, it improves the structural and functional properties of pancreatic β-cells, hence bolstering the long-standing application of Cryptolepis sanguinolenta in the management of diabetes.

CLINICAL VALIDATED USES   

TYPE 2 DIABETES TREATMENT

In a study involving eight women with Type 2 diabetes, treatment with Cryptolepis sanguinolenta extract led to a significant reduction in fasting blood glucose levels, decreasing by approximately 4 mmol l−1. Notably, there were no observed changes in body weight or clinical symptoms of toxicity among the participants. Each participant was administered a daily dose of 7.3 mg of the extract, which provided a dosage of 0.11 mg kg−1 day−1 of cryptolepine.

TREATMENT OF UPPER RESPIRATORY TRACT, URINARY INFECTIONS AND MALARIA

Oku Ampofo of the Centre for Scientific Research into Plant Medicine in Ghana has been using a root decoction in clinical therapy for upper respiratory tract infections, malaria, and urinary tract infections since 1974.

TREATMENT OF MALARIA

A tea-bag formulation of Cryptolepis sanguinolenta root was tested for its clinical effectiveness and safety in treating acute, uncomplicated falciparum malaria. Results showed all patients recovered by Day 7, 50% within 72 hours, and a total cure rate of 93.5%, with no toxicity detected.

DRUG-DRUG INTERACTION

SYNERGISTIC EFFECT

Dipyridamole and the ethanol carrier improved the synergistic antithrombotic effects of Cryptolepis sanguinolenta.

INHIBITORY EFFECT

Small doses of cryptolepine had their potentiative effects countered by cocaine, indicating that the mechanism involved was suppression of neuronal noradrenaline absorption. Also, dihydro artemisinin's clearance and elimination rate constant increased by 233.3% and 62.1%, respectively, after administration of Cryptolepis sanguinolenta. However, its bioavailability, volume of distribution, and half-life were reduced by 41.1%, indicating that sub-therapeutic blood levels may result in drug resistance.

TOXICOLOGICAL PROFILE

Sprague-Dawley rats treated with extract dosages up to 3000 mg/kg showed no acute behavioral or physiological changes, but subacute toxicity revealed increased granulocyte and platelet counts, inflammation, and liver and kidney enlargement. Cryptolepis sanguinolenta root extract has been found to cause severe reproductive and developmental toxicity in test animals, indicating caution when used during pregnancy and in males. Cryptolepine, an alkaloid from Cryptolepis sanguinolenta, can cause morphological defects, death, and hatching inhibition in zebrafish embryos, hindering development and causing teratogenicity.  The root extract of Cryptolepis sanguinolenta yielded an LD50 of 758.5 mg/kg body weight in the acute toxicity test.

 

 

 

 

 

 

 

 

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