Faculty of Health Sciences

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Evaluation of selected South African medicinal plants in the treatment of pre-eclampsia
(2023-05) Reddy, Rebecca; Govender, Nalini; Naicker, Thajasvarie
Background: The growing prevalence of pre-eclampsia (PE) has been recognized as a serious global health threat being a key contributor to maternal and feotal morbidity and mortality. Locally, the effects of PE are multiplied due to strained public healthcare resources. The need for novel therapeutic strategies has gained significant importance, as conventional options may be inaccessible and costly to a large percentage of the population and are often associated with side effects. The scientific validation of alternative approaches, such as phytotherapy, has become a major focal point in the treatment and management of PE, as it is perceived to be cheap, accessible, and possess minimal side effects. Medicinal plants are a rich source of phytocompounds that display various biological activities. Hence, these plants have gained interest within the field of novel drug discovery and may offer potential therapeutic benefits in managing PE and its associated complications. Aim: This study aimed to determine the potential of applications of South African medicinal plants in the management of PE by investigating their anti-oxidative and angiotensin-converting enzyme (ACE) inhibitory activities. The plants used in this study were Artemisia afra, Clausena anisata, Dombeya rotundifolia, Rhus chirendensis, Sclerocarrya birrea and Warbugia salutaris, as well as phytocompounds 3β-taraxerol, β-amyrin, oleanolic acid, hesperidin, nicotinamide, and quercetin for the treatment of PE. We then explored the anti-hypertensive properties of hesperidin in a novel rodent model of PE as a potential treatment option. Methodology: The methanolic extracts of the selected plants and phytocompounds were initially evaluated in vitro for their antioxidant potential and ACE inhibition activities using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, the nitric oxide (NO) scavenging assay and the ACE inhibition assay, respectively. To investigate in vivo effect of the hesperidin, Sprague-Dawley rats were surgically implanted with mini-osmotic pumps to deliver arginine vasopressin (200 ng/h) subcutaneously to create a PE phenotype. Animals were treated with hesperidin (200mg/kg.b.w) via oral gavage for 14 days and the physiological effects were characterized by evaluating the clinical, biochemical, hematological, and foetal parameters across all experimental groups. Key findings: Of the medicinal plants and phytocompounds evaluated, Dombeya rotundifolia, hesperidin, and nicotinamide demonstrated significant ACE inhibitory and antioxidant activity, showing the best potential for management of PE related symptoms. Hesperidin administration alleviated the AVP-induced hypertension associated with PE development and improved maternal and foetal outcomes. Placental and individual pup weights were significantly increased in the pregnant hesperidin-treated groups. Urinary protein and urine creatine levels were also significantly improved following treatment with the phytocompound. In addition, hesperidin improved several biochemical and hematological markers including white blood cell counts and lymphocyte levels. Conclusion: Our findings suggest the potential of medicinal plants to ameliorate oxidative stress-associated disorders. Furthermore, hesperidin improves physiological outcomes in a novel AVP-induced rodent model and support its potential use in the treatment of PE. We provide significant physiological evidence for the use of hesperidin as an alternate anti-hypertensive agent, in resource-limited areas where conventional drugs are often costly and inaccessible. Moreover, we provide a workflow for evaluating other potential phytochemicals that may be valuable in the treatment of hypertensive disorders of pregnancy.
The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study
(Wiley, 2016-10-03) Dorsamy, V.; Vallen, C.; Haffejee, Firoza; Moodley, J.; Naicker, T.
Objective To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. Design Cross-sectional immunohistochemical analysis of target receptor expression. Setting Laboratory-based study of primigravidae attending a district hospital in South Africa. Population or sample Retrospectively collected placental tissue (stratiﬁed into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group). Method Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis. Main outcome measures Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV. Results Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159 = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159 = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was signiﬁcantly higher in the HIV-negative pre-eclamptic group (v2 (3) = 45.3; P < 0.001). Conclusion Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may inﬂuence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further conﬁrmatory ultrastructural and molecular work is warranted.
Placental leptin mRNA expression and serum leptin levels in pre-eclampsia associated with HIV infection
(Taylor and Fancis Online, 2016-10-03) Haffejee, Firoza; Naicker, Thajasvarie; Singh, Moganavelli; Kharsany, Ayesha B.M.; Adhikari, Miriam; Singh, Ravesh; Maharaj, Niren; Moodley, Jagidesa
Leptin, primarily produced by adipocytes, is implicated in the development of pre-eclampsia. This study examines placental leptin production and serum leptin levels in HIV infected and uninfected normoten-sive and pre-eclamptic pregnancies. Placental leptin production was analysed by RT-PCR and serum lep-tin levels by ELISA in normotensive (n ¼ 90) and pre-eclamptic (n ¼ 90) pregnancies which were further stratified by HIV status. Placental leptin production was higher in pre-eclampsia compared to normoten-sive pregnancies irrespective of HIV status (p ¼ .04). Serum leptin was non-significantly raised in HIV uninfected (p ¼ .42) but lower in HIV-infected (p ¼ .03) pre-eclampsia. The latter had lower BMI (p ¼ .007) and triceps skin-fold thickness (p < .001) than the HIV uninfected groups with a significant correlation between serum leptin and triceps skin-fold thickness (p < .001), indicative of less adipose tissue in HIV-infected women with consequently lower serum leptin. Thus, serum leptin levels are not indicative of increased placental production when pre-eclampsia is associated with HIV infection.

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