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Review Article
 

Leptadenia hastata Pers. (Decne) a Promising Source for Natural Compounds in Biomedical Applications



Bayala Balé, Halabalaki Maria, Ouedraogo Amadé, Keiler Martina Annekathrin, Tamboura Hamidou Hamadou and Vollmer Günter
 
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ABSTRACT

Leptadenia hastata (Pers) Decne. of Apocynaceae family is an African plant which is used as nutriment as well as for medical purposes due to its health promoting properties. Traditional healers use L. hastata to treat many diseases as hypertension, sexual impotence, trypanosomosis, acute rhinopharyngitis. In quantitative and qualitative terms, the leaves of L. hastata contain significant quantities of secondary metabolites, as triterpenes, total flavonoids, tanins, which can be important in biomedical research. In vivo studies showed the antifertility effect of L. hastata leaves extracts which can be useful for hormonal therapy replacement. Herein, the ecology, traditional medicinal uses, phytochemistry, toxicity and pharmacology of L. hastata in consideration of its antifertility activity is reviewed. In view of its constituents such as steroidal glycosides, triterpenes and polyoxypregnane derivatives, further investigation on the effect of L. hastata on other hormonal endpoints like hormone dependent cancers appears promising.

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Bayala Balé, Halabalaki Maria, Ouedraogo Amadé, Keiler Martina Annekathrin, Tamboura Hamidou Hamadou and Vollmer Günter, 2018. Leptadenia hastata Pers. (Decne) a Promising Source for Natural Compounds in Biomedical Applications. American Journal of Drug Discovery and Development, 8: 1-10.

DOI: 10.3923/ajdd.2018.1.10

URL: https://scialert.net/abstract/?doi=ajdd.2018.1.10
 
Received: March 08, 2018; Accepted: August 30, 2018; Published: November 09, 2018

INTRODUCTION

The interest of Africans in plants as source of potential remedies exists for thousands of years. Until now, more than 80% of the African population use single or combined plant extracts for their everyday health care needs. This is not only due to African poverty but also because of the richness of African plant species that have healing properties, known throughout the ages1.

Leptadenia hastata (Pers.) Decne. (L. hastata) is a perennial liana species of the Apocynaceae family that includes the subfamily Asclepediaceae2-4. Asclepiadaceae plants are widely used in traditional medicine and have been reported to be rich in steroidal glycosides, cardenolides, flavonoids, triterpenes and polyoxypregnane derivatives5-9.

Leptadenia hastata is an important emergent local food of Africa with the ability to grow under harsh environmental conditions10. Many studies have revealed the potential of L. hastata for different uses11-13. It is worth to be noticed that hormone-like activities of L. hastata have been reported in response to the administration of its extracts with regard to the weight of reproductive organs, spermatogenesis and testosterone levels14,15. However, despite its widespread distribution, traditional medicinal applications and rich chemical content, data on its phytochemistry and pharmacology have been only partially summarized so far16,17. Considering the wealth of L. hastata regarding steroidal compounds, the aim of this review is to assess phytochemical and pharmacological data available on L. hastata towards additional hormone-related conditions like hormone-dependent cancers and hormone deficiency syndromes.

NATURAL COMPOUNDS IN BIOMEDICAL APPLICATION

Botanical aspects: The genus Leptadenia R. Brown comprises 4 species: L. arborea (Forssk.) Schweinf., L. madagascariensis Decne., L. hastata (Pers.) Decne. and L. pyrotechnica (Forssk.) Decne. L. arborea is a slender liana of scrub vegetation, distributed from West Africa to Arabia in Sahelian areas18. It provides excellent forage for all livestock and is recognized to have medicinal properties18,19. L. pyrotechnica is an erect leafless shrub which grows on sand dunes and is widespread from Senegal to India. The latex and seeds of this shrub are of medicinal value and young shoots are used as vegetable20. L. madagascariensis is an endemic liana from Madagascar dry forests, where its mature leaves serve as fodder for lemurs and also used for medicine purposes21,22.

Leptadenia hastata is a latex-containing herb at young stage and becomes woody liana when getting old, thereby developing a strongly branched climbing stem (Fig. 1a, b).

Fig. 1(a-b): Leptadenia hastata (a) Young stage and (b) Woody corky stems at adult stage (Photo BBale)

The finely pubescent branches get corky with age. The leaves of L. hastata are opposite and simple with petiole, variable limb shape, usually ovate, rounded or cordate at the base. The limb has an acuminate apex, an entire margin and both sides glabrous or finely pubescent. The inflorescences are umbellate with several flowers arranged on 1.5 cm long peduncle (Fig. 2). The Flowers are bisexual, regular 5-merous, yellowish and scented; corolla with 5 pubescent lobes. The fruit is a pair of follicles, each one is conical with a length up to 10 cm. The seeds carry a tuft of hairs at the apex20.

Ecology Aspects: Leptadenia hastata is a common species in the sahelo-sudanian semi-arid area of West Africa.

Fig. 2: Inflorescences and flowers of Leptadenia hastata (Photo. Bbalé)

It grows on all types of soils and is a pioneer species of bare soil restoration in the Sahel23-25. Leptadenia hastata reproduces by seeds that are widely dispersed by wind. Occasionally, it is intentionally sown near houses so that it is available for human consumption. Leptadenia hastata is frequently parasitized by the aphid Aphis nerii, which is predated by the coccinellid Cydonia vicinia. This latter species has been used to biologically control Aphis craccivora, Aphis gossypii and Melanaphis sacchari which are known to cause transmission of rosette disease of groundnut and to attack sorghum and cotton.

Traditional medicinal uses: Various parts or constituents of L. hastata have been described for the application in traditional medicinal applications (Table 1). The latex is applied on wounds and put in the nose against headache. Decoctions and macerations of roots and leaves are applied both, alone or in combination with other plants against abdominal complaints such as constipation, urethral discharge, gonorrhoea, stomachache and diarrhoea12. An extract of boiled leaves and stem is drunk regularly to treat dyspepsia and hemorrhoids. Ethnobotanical information from traditional medical practitioners in northern Nigeria revealed that L. hastata aqueous extracts are used for the treatment of diabetes mellitus26.

The plant is used in herbal medicine against milk drying, sexual impotence, trypanosomosis and acute rhinopharyngitis27. The leaves are often chewed by shepherds against polydipsia and mouth dryness28. To treat nausea28 three soup spoons full of a decoction are taken which is prepared from two handfuls of fresh leaves and boiling in about 500 mL of water until the fluid is reduced to half.

In Mali, traditional healers treat onchocerciasis with L. hastata leaves decoction and Erythrina senegalensis bark29. The roots are taken against scabies in Chad and, in Nigeria, local healers use the whole plant against hypertension and skin diseases30.

In veterinary medicine, L. hastata is used to treat horse’s colic. In addition, antibacterial and antimicrobial effects of L. hastata have been reported31. Safety studies revealed no acute toxicity from L. hastata water extract suggesting that use of the plant is relatively safe24.

Chemical component of L. hastata: L. hastata is characterized by significant quantities of a variety of essential nutrients11-14 (Table 2), justifying its important role as nutriment. Fatty acids, vitamin E, carotenoids, selected minerals and amino acids have been also determined in the leaves of L. hastata, particularly rich in lutein and beta-carotene32. So far, it is distinguished by the presence of terpenoids and saponins since the phytochemical data are rather limited. There is only a small number of studies related to the isolation and identification of secondary metabolites from L. hastata.

Specifically, the separation, purification and structural elucidation of six new polyoxypregnane esters and three new glycosides was accomplished together with five known esters from the CHCl3 extract of the bark of L. hastata33 (Fig. 3). The bark of L. hastata plant is used as an anti-inflammatory and antitumor drug in Senegalese folk medicine34.

Further investigations of the most polar extracts (CHCl3/MeOH 9:1 and MeOH) have led to the isolation of 34 new related esterified aglycones and glycosides (Fig. 4). The structures of these compounds are based on the known polyoxypregnane skeleton of sarcostin or deacetyl metaplexigenin as well as acetyl, benzoyl, cinnamoyl, nicotinoyl and m-hy-droxybenzoyl ester moieties linked at C-12 and/or at C-20 of the aglycones. In addition, the glycosides that possess an oligosaccharide portion linked at C-3 to the aglycones consist of three to five deoxyhexopyranoses and hexopyranoses, sugars well known to occur in Asclepiadaceae plants35.

Table 1: Overview of traditional medicinal uses of Leptadenia hastata

Table 2: Nutrient composition of Leptadenia hastata10-13
Ca: Calcium, Cr: Chromium, Cu: Copper, Fe: Iron, K: Potassium, Mg: Magnesium, Mn: Manganese, Mo: Molibdène, Na: Sodium, Ni: Nickel, P: Phosphor, Se: Selenium, Zn: Zinc

L. hastata is well known to be a good source of triterpenes. Triterpenes are a huge class of chemical compounds produced by arrangement of squalene epoxide in a chair-chair-chair-boat arrangement followed by condensation. As cholesterol does in animal cell membranes, free triterpenes can stabilize phospholipid bilayers in plant cell membranes. One triterpene which has gained wide attention of medical professionals, pharmaceutical marketers and researchers all around the world, is Lupeol (Fig. 5). Lupeol was isolated from the latex of L. hastata for tests on anti-inflammatory activities13.

The evaluation of the phenolic compounds of L. hastata leaves indicated the presence phenolic glycosides, tannins, flavonoids, proanthocyanidins, alkaloids and saponins.

Fig. 3: Polyoxpregnane esters and new glycosides isolated from the bark of L. hastata

According to the extraction solvent, the amount of phenolics was more important and ranged in 17-38 mg g1 compare to the amount of total flavonoids and proanthocyanidins which was in the ranges of 10-16 and 4-10 mg g1 respectively26.

Toxicology of Leptadenia hastata: Although, L. hastata is used as food, the acute toxicity of the aerial parts has been evaluated in male albino mice24. The orientation test showed that LD50 values varied between 1000 and 2000 mg kg1. The trial conducted on 6 groups of 6 mice each showed a LD50 value of 1512.879 mg kg1 for L. hastata aqueous extract. Signs of intoxication observed were polypnea and asthenia. The ratios of LD5/LD50 and LD50/LD95 are similar and confirmed the validity of LD50 test values. The value 0.78 for the quotient LD5/LD95 proves that L. hastata is very safe for use.

L. hastata leaves were shown to contain a trypsin inhibitor which is an anti-nutrient element. Before boiling the leaves, their content was 0.25 μg mg1 and after boiling the leaves contained 0.18 μg mg1 of the trypsin inhibitor. This trypsin inhibitor was 72% resistant to boiling. This caveat is based on the possible co-presence of protease inhibitors in the ingested L. hastata leaves, inhibitors that might reach the small intestine and block the activity of proteases, such as trypsin, that normally catalyze the hydrolysis of dietary proteins, an obligatory step in the process of protein digestion and absorption36.

Pharmacological studies: Several studies were conducted to elucidate the biological activities of L. hastata extracts. Most of them were focused on anti-inflammatory and anti-bacterial effects of the extracts.

The acetone, methanol and aqueous extracts of L. hastata leaves were investigated against five selected bacterial species and two fungal species31. The aqueous extract markedly inhibited the growth of Salmonella paratyphi and Escherichia coli at 30 mg mL1 and Pseudomonas aeruginosa at 60 mg mL1. The activity of the methanolic extract was generally low and the acetone extract did not show any activity against the investigated organisms. The results of anti-mycotic assay showed that the methanol extract suppressed the growth of Fusarium oxysporum and Aspergillus niger at 80 mg mL1 with inhibition percentages ranging from 59-73%. The activity of the acetone extract was low with 40 and 50% inhibition on the growth of A. niger and F. oxysporum, respectively.

Fig. 4: Esterified aglycones and glycosides from L. hastata

Very few studies showed anti-fertility activities of L. hastata although, in some parts of Africa, many breeders claim the loss of fertility of their animals after consumption of L. hastata leaves.

Fig. 5:

Lupeol isolate from L. hastata latex

Fig. 6: Effect of Leptadenia hastata extracts on sperm number in testis and cauda epididymis
  *p<0.05, **p<0.001)48

Literature surveys and ethnobotanic investigations with traditional healers revealed that the consumption of L. hastata leaves by donkeys, horses and dromedaries can compromise fertility.

In Linguere, Senegal, some abortions on horses and dromedaries are linked to L. hastata ingestion. To evaluate the abortifacient properties of L. hastata in mice, pregnant mice were fed a diet substituted with 25 and 50% of a powder of the aerial parts of L.hastata37. The results obtained showed that reproduction rates are significantly reduced in groups fed with 25 and 50% of L. hastata if compared to control groups. From those results, it was concluded that L. hastata causes partially abortion in mice, probably by a toxic effect leading to the death and the resorption of the embryo.

For the north regions of Burkina Faso, it was also reported that the consumption of L. hastata leaves had harmful effects on the fertility of sheep and goats38,39.

If tested in male rats, L. hastata aqueous extracts reduced significantly the weight of androgen dependent accessory reproductive glands, the content of Prostatic acid Phosphatase (PAP) and fructose in seminal vesicles and prostate, as well as the serum testosterone level. When Testosterone Propionate (TP) was simultaneously administered with 100, 200 and 400 mg kg1 of L. hastata aqueous extracts in a dose-dependent manner, a potentiation of TP action with the dose of 100 mg kg1 of L. hastata was observed. This effect was detectable by a weight increase of androgen-dependent accessory reproductive glands, fructose and PAP levels in seminal vesicles and prostate and on the serum testosterone level. An anti-androgenic effect of L. hastata in a combinatorial experimental setting with TP appeared at doses of 200 and 400 mg kg1 b.wt., which significantly reduced the experimental parameters specified above. Overall this can be interpreted as mixed agonistic/antagonistic properties of L. hastata extracts40.

Circulating levels of testosterone are required for the maintenance of accessory sex organ function but the threshold levels of required hormone might be different for different functions and may be species-specific. The L. hastata aqueous extracts can inhibit androgen function through multiple mechanisms41,42, antagonism of androgen receptors43 and inhibition of testosterone production by increasing testosterone turn-over and elimination through induction of metabolic enzymes. Also, it is conceivable that L. hastata extracts may contain phytoestrogen-like activities: The potential role of phytoestrogens on male fertility has been attributed to both estrogenic and anti-estrogenic properties44. These observations could explain the loss of fertility of animals consuming the leaf stems of L. hastata which might be induced by non-steroidal compounds with anti-androgenic properties. Anti-androgens may have many implications in the regulation of animal reproduction45 and may be useful for the treatment or prevention of prostate cancer. All currently applied anti-androgen therapies of prostate cancer are based on the reduction of the accessibility of the receptor by the ligand, either by a competitive antagonism on the level of the receptor or indirectly by inhibition of androgen production. Limitations of these therapies are acquired resistance and serious side-effects46,47.

Male rats exposed to L. hastata presented a decreased number of sperm (Fig. 6)48. It is well established that androgens and gonadotropins are essential for the spermatogenesis and the function of male reproductive system49. The decrease of the number of sperm in rats treated with plant extracts may be derived from a hormonal imbalance including serum levels of testosterone, prolactin and LH. Low cauda epididymal and testis sperm count and a reduction in the epididymis and testis weight imply that effects following exposure to L. hastata aqueous extracts might be caused by several factors. One factor may be that L. hastata extract interferes with enzymatic reactions including the oxidative phosphorylation uncoupling50,51.

It is a known and a widely accepted concept that Luteinizing Hormone (LH) is basically responsible for testosterone production in animals52. One plausible explanation may be the suppression of LH as the primary step in the mechanism of the effects of the L. hastata extract on testis. At the testicular level, the absence of stimulation by LH would secondarily cause Leydig cell dysfunction, which, as a consequence, results in the decline of testosterone secretion and this in turn is responsible for the impairment of spermatogenesis and hence reflected by the reduction in sperm counts53-55. In addition, the structure and the function of the epididymis are dependent on androgens56. The suppression of cauda epididymal sperm motility suggests an under-supplementation of the epididymis with testosterone and, therefore, leads to an impaired epididymal function. The impaired epididymal function may also be due to the reduction of the testicular activity which affects the normal passage of testicular fluid into the epididymis48,49. Finally, this phenotype is also in part consistent with an Estrogen Receptor-α (ERα) deficiency or with phenotypes observable following treatment of animals with a pure antiestrogen57.

Normal and alloxan induced diabetic rat models were used to assess the hypoglycaemic and hypolipidaemic effects of L. hastata water and methanol extracts. The results are showed with oral administration, the decreased of blood glucose and the increase of liver and muscle glycogen levels at the dose of 300 mg kg1. There was also an increase in high density lipoprotein cholesterol levels and a reduction of serum triglyceride, very low-density lipoprotein cholesterol levels27.

CONCLUSION

Leptadenia hastata plays a very important role as a medicinal plant. Its ecology shows that this plant is a non-cereal and non-cultivated plant in the Sahel regions. Toxicological and pharmacological studies showed negligible general toxicity and anti-inflammatory and anti-bacterial activities. The effect of the leaves extracts on rat and mice showed an anti-androgenic and abortifacient properties pointing to potential hazards regarding reproductive toxicology. All these activities are due to the rich diversity of the chemical constituents of L. hastata.

In view of the composition of L. hastata in steroidal glycosides, triterpenes and polyoxypregnanes, it will be promising to evaluate the plant towards additional hormone-related conditions like hormone-dependent cancers and hormone deficiency syndromes.

SIGNIFICANCE STATEMENT

This study shows the medicinal, phytochemical and biological potentialities of L. hastata which can be beneficial in hormonal replacement therapy. L. Hastata is a food plant immensely spread in western and center of Africa with an extremely weak toxicity. This study will help the researchers to take L. hastata as a biological material for the biomedical research for hormono-dependent cancers.

ACKNOWLEDGMENT

The present work has been done with the support from Alexander Von Humboldt Foundation in Germany.

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