Chromatographic Enrichment Of Bioactive Quassinoids In Tongkat Ali For The Improvement Of Spermatogenesis

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dc.contributor.authorChung, Wan Jie
dc.date.accessioned2021-02-15T02:33:55Z
dc.date.accessioned2021-02-15T02:33:59Z
dc.date.available2021-02-15T02:33:55Z
dc.date.available2021-02-15T02:33:59Z
dc.date.issued2018-09
dc.description.abstractEurycoma longifolia Jack roots, traditionally used as herbal remedies for increasing libido and better health conditions, contain a high content of quassinoids, the bitter substances and alkaloidal canthinones, indigenous in the Simaroubaceae family that are responsible for the plant pharmacological properties. Amongst the quassinoids, the 20-carbon eurycomanone (EN), 13α(21)-epoxyeurycomanone (EP), eurycomanol (EL) and 13α,21-dihydroeurycomanone (DHY), possess anti-malarial, anti-ulcer, anti-pyretic, anti-osteoporosis, aphrodisiac and anti-infertility properties. In the present study, the chromatographic separation employing macroporous resin Diaion HP-20, Sepabeads SP-700 and SP-207 were evaluated for the enrichment of EN and DHY in E. longifolia methanolic extract. Results showed that among the three macroporous resin, Diaion HP-20 performed the best enrichment and separation characteristics. After single chromatographic fractionation with Diaion HP-20, the content of EN and DHY were increased from 6.13 % and 0.54 % to 30.40 % to 13.96 % w/w, respectively. Meanwhile, a simple and reliable high performance liquid chromatography with ultraviolet detection method was developed and validated for the determination of EN and DHY. Subsequently, the EN-rich and DHY-rich fractions were subjected to pharmacokinetic evaluation in rats. The present finding indicated that DHY was able to achieve a higher peak concentration (Cmax) and total area under the curve (AUC0-∞) compared to those of EN in oral dosing. The absolute bioavailability of both compounds remained low (< 5 %) but DHY showed a significantly higher bioavailability (1 %) than EN (0.3 %) which may be attributed to the slightly higher lipophilicity of DHY. Subsequently, the EN-rich and DHY-rich fraction were tested for in vivo spermatogenesis activity. Sperm, count, motility and morphology at the cauda epididymal of the rats were carried out. The animals treated with EN-rich fraction scored the highest increase in sperm count of 48.60 x 106/mL/g of testis, followed by DHY-rich treated rats (39.24 x 106/mL/g of testis) and control group (25.87 x 106/mL/g of testis), suggested that EN was more potent than DHY in the improvement of spermatogenesis. However, there were no significant difference in sperm motility and morphology among the treated rats and control group. In addition, an oligospermic rat model was designed by using andrographolide isolated from Andrographis paniculata to evaluate the efficacy of EN and DHY in the augmentation of abnormal spermatogenesis. Oligospermic rats administered with EN-rich fraction (37.69 x 106/mL/g) and DHY-fration (30.08 x 106/mL/g) reported significant (P < 00.5) increase in sperm count compared to the negative control group given andrographolide only. In conclusion, despite DHY having a three-fold higher oral bioavailability than EN, EN-rich fraction was more potent in enhancing sperm production than DHY-rich fraction. These results indicated that the bioactivity of the quassinoids may be governed not only by the pharmacokinetic and physicochemical factors but also pharmacodynamics factors such as their intrinsic molecular interaction with the target site of action.en_US
dc.identifier.urihttp://hdl.handle.net/123456789/11245
dc.language.isoenen_US
dc.publisherUniversiti Sains Malaysiaen_US
dc.subjectMedicinal plantsen_US
dc.subjectSpermatogenesisen_US
dc.titleChromatographic Enrichment Of Bioactive Quassinoids In Tongkat Ali For The Improvement Of Spermatogenesisen_US
dc.typeThesisen_US
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