Seasonal variations of essential oil composition and some biological evaluation of Pelargonium inquinans (L.) Ait. South Africa

Pelargonium inquinans which belongs to the family Geraniaceae, is an essential oil yielding plant. P. inquinans was collected from two different sites in Grahamstown (wild) and Alice, at the University of Fort Hare botanical garden. Authentication of the plant was done by Dr. T. Dold at Schonland herbarium, and the voucher specimen being T01. This study is focused at determining the chemical constituents and biological properties of the essential oils of wild and cultivated P. inquinans across different seasons, as the plant grows throughout the year. Seasonal collection of wild and cultivated P. inquinans was achieved in a duration of 12 months. 32 essential oil samples of P. inquinans were obtained by extraction using hydro-distillation technique for 3-4 hours. The chemical composition of the essential oils was determined using GC/MS and GC/FID. Amongst the 32 essential oils only 4 samples wild ( fresh stem and leaf) and cultivated ( fresh stem and leaf) from summer season were evaluated for analgesic activity using acetic acid induced writhings and hot plate nociception models in mice, anti-inflammatory activity was determined on the egg albumin- induced rat paw oedema in rats. The results obtained from GC-MS revealed a total of 169 components obtained from the leafstem, fresh/dry wild and cultivated P. inquinans. These essential oils showed a great deal of chemotaxonomic variation and similarity in the major and minor components along the season. In spring season the essential oils of wild and cultivated P. inquinans had abundance of hydrogenated sesquiterpenes (20.6percent-66.7percent). The major components were found to be α-caryophyllene (9.1percent-26.8percent), p-xylene (23.3percent-27.5percent), β-caryophyllene (11.4percent-30.9percent), o-xylene (6.3percent-39.4percent), β-thujene (8.7percent), isocaryophyllene (13.9percent), isoborneol (14.2percent), β-myrcene (5.7percent), geranyl acetate (13.8percent), toluene (7.9percent), β-gurjunene (18.5percent), α-cadinene (15.8percent), β-farnesene (14.2percent), 3-carene (12.1percent) and camphene (9.0percent). In summer season the essential oils of wild and cultivated P. inquinans were found to have abundance of hydrogenated sesquiterpenes (50.3percent- 63.0percent), oxygenated monoterpenes (30.4percent) and hydrogenated monoterpenes (20.8percent- 61.0percent). The major components were found to be α-caryophyllene (12.3percent-25.8percent), β-caryophyllene (15.1percent- 31.7percent), trans-caryophyllene (10.3percent- 17.8percent), phytol (14.2percent- 20.2percent), camphor (46.5percent), sabinene (27.8percent), elemol (18.1percent), z3-hexenyl isobutyrate (16.3percent), limonene (12.1percent), menthone (12.1percent)< E.E-β-farnesene (14.7percent), palmitic acid (9.6percent), eugenol (9.4percent), cis- β-ocimene (8.7percent), α-terpineol (8.7percent), geranyl acetone (7.8percent), β- humulene (7.5percent). linoleic acid (7.4percent), trans-linalool oxide (7.4percent), β-bisabolene (7.1percent), cis- linalool oxide (7.1percent), ionone (6.9percent), caryophyllene oxide (6.9percent) and germacrene d (6.3percent). In autumn season the essential oils of wild and cultivated P. inquinans were found to be rich in hydrogenated sesquiterpenes (29.3percent- 65.2percent) and oxygenated sesquiterpenes (22.8percent- 31.4percent). The major components were found to be α-caryophyllene (15.5percent- 23.4percent), β-caryophyllene (15.2percent- 17.2percent), β-myrcene (7.7percent-13.8percent), β-humulene (8.7percent- 15.2percent), caryophyllene oxide (9.8- 16.2percent), trans- caryophyllene (16.7percent- 23.3percent), α-humulene (11.8percent- 18.6percent), linoleic acid (11.2percent), palmitic acid (10.4percent), phytol acetate (8.5percent), -longipinene (8.3percent) and citronellol (7.8percent). In winter season the essential oils of wild and cultivated P. inquinans were found to have abundance of hydrogenated sesquiterpenes (25.1percent- 48.6percent), oxygenated monoterpenes (47.6percent), oxygenated sesquiterpenes (22.2percent- 28.0percent). The major components were found to be β-caryophyllene (14.6percent- 23.0percent), α-caryophyllene (9.4percent- 18.0percent), trans- caryophyllene (12.2percent- 14.6percent), α-cedrene (26.2percent), germacrene –d-4-ol (16.8percent), 2,6-dihydroxyacetophenone (15.6percent), (+) epibicyclosesquiphellandrene (15.3percent), E-β- farnesene (13.0percent), β-phellandrene (11.7percent), 2-nitrophenol (9.5percent), palatinol (8.4percent), geranyl acetate (7.7percent) and linoleic acid (7.4percent). The oils from the wild and cultivated sources showed significant (p<0.05-0.001) decrease in number of writhes induced by the acetic acid compared to vehicle; caused significant (p<0.05-0.001) delay in reaction time on the hot plate at 60 and 90 min post-treatment and significantly (p<0.05-0.001) reduced oedema size caused by the egg albumin injection compared to the vehicle. The oils from the wild plant showed more potency compared to the cultivated. The essential oils of wild and cultivated P. inquinans showed qualitative, quantitative and chemotaxonomic variation with analgesic and anti-inflammatory activity. These essential oils need to be explored for further biological analysis because of the major components they contain

HPLC-based purification and isolation of potent anti-HIV and latency reversing Daphnane Diterpenes from the medicinal plant Gnidia sericocephala (Thymelaeaceae)

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The “shock and kill” therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 g/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 M without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.SUPPLEMENTARY MATERIAL : TABLE S1: Anti-HIV replication activity of the positive control efavirenz using the in vitro deCIPhR assay: TABLE S2: Anti-HIV replication activity of G. sericocephala root extracts using the in vitro deCIPhR assay: TABLE S3: Cytotoxicity of G. sericocephala root extracts using the in vitro deCIPhR assay; FIGURE S1: 1H NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S2: 13C NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3): FIGURE S3: The DEBT NMR data of yuanhuacine A (1), acquired on a Bruker Avance III HD 500 MHz NMR spectrophotometer with Prodigy Probe, the compound dissolved in deuterated chloroform (CDCl3).Funding was provided by the South African Department of Science and Innovation (DST/CON 0031/2019), Canadian Institutes for Health Research (CIHR PJT-153057) (I.T.) and the New Frontiers in Research Fund—Explorations (NFRFE-2018-01386) (I.T.). This work was also supported through the Sub-Saharan African Network for TB/HIV Research Excellence (SANTHE) (I.T.; N.G.), a DELTAs African Initiative [grant # DEL-15-006]. The DELTA African Initiative is an independent funding scheme of the African Academy of Sciences (AAS)’s Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa’s Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Welcome Trust [grant # 107752/Z/15/Z] and the UK government. This work was also supported by grants to L.J.M.: Beyond Antiretroviral Treatment (BEAT)-HIV Delaney Collaboratory Grants UM1AI126620 and UM1AI64570. It was also supported by the Robert I. Jacobs Fund of the Philadelphia Foundation; Penn Center for AIDS Research Grant P30 AI 045880; and the Herbert Kean. The APC was funded by University of Pretoria and Deaprtment of Science and Innovation.https://www.mdpi.com/journal/virusesam2023Chemistr

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae)

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The &ldquo;shock and kill&rdquo; therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by &gt;80% at 0.08 &micro;g/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 &micro;M without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions

Characterization and isolation of anti-HIV and latency reversal agents for the development of a herbal mixture

This is data for a descriptive research that describes the methods carried out on the  latency reversal activity of G. sericocephala is found in supplementary data 1. The ultra-performance liquid chromatography tandem mass spectrometry spectral data  of the solvent blank is shown in supplementary 2. Supplementary data 3 contains the ex vivo anti-HIV activity in PBMC’s. Supplementary data 4 is a summary of mean of Summary of mean potency values (IC50 ± S.D.), inhibition values at each test concentration, for the test samples, the positive control, verapamil, potency. All data in tables are expressed as mean inhibition or mean µM potency, from N ≥ 3 separate cells. The positive control value was within the acceptable potency range (0.2 - 0.8 µM). The tandem mass spectral data of lasioerin shown in supplementary 5. The nuclear magnetic resonance spectra of lasioerin are shown in supplementary data (6-11). The compound lasiocephalin  nuclear magnetic spectral data is shown in supplementary data (12-15). Supplementary data 16 shows the tandem mass spectral data of yuanhuacine A. While the nuclear magnetic resonance spectroscopy is shown in supplementary data (17-23). The compound yuanhuacine mass spectral data is shown in supplementary data 24. While the nuclear magnetic resonance spectroscopic data of yuanhuacine is shown in supplementary data (25-30). The mass spectral data of cis 2′′/3′′ isomer of gnididin is shown in supplementary data (31). While the supplementary data of cis 2′′/3′′ isomer of gnididin is shown in supplementary data (32-37). The compound yuanhuajine has its mass spectral data shown in supplementary data 38. While the nuclear magnetic spectral data of cis 2′′/3′′ isomer of gnididin is shown in supplementary data (39-42). The mass spectral data of the compound gniditrin and its proton nuclear magnetic spectral data are shown in supplementary data 43 and 44, respectively. </p

Evaluation of Trace Metal Profile in Cymbopogon validus and Hyparrhenia hirta Used as Traditional Herbs from Environmentally Diverse Region of Komga, South Africa

FAAS was used for the analysis of trace metals in fresh and dry plant parts of Cymbopogon validus and Hyparrhenia hirta species with the aim of determining the trace metals concentrations in selected traditional plants consumed in Eastern Cape, South Africa. The trace metal concentration (mg/kg) in the samples of dry Cymbopogon validus leaves (DCVL) showed Cu of 12.40±1.000; Zn of 2.42±0.401; Fe of 2.50±0.410; Mn of 1.31±0.210; Pb of 3.36±0.401 mg/kg, while the samples of fresh Hyparrhenia hirta flowers (FHHF) gave Cu of 9.77±0.610; Zn of 0.70±0.200; Fe of 2.11±0.200; Mn of 1.15±0.080; Pb of 3.15±0.100 mg/kg. Abundance of metal concentrations follows the order: Cu > Fe > Pb > Mn > Zn in the flower samples of Cymbopogon validus and Hyparrhenia hirta species. The concentrations of trace metals in both plant parts were below the permissible limits (PL) set by WHO. It is suggested that pharmacovigilance be carried out periodically to improve the quality, safety, and efficiency of various herbal products

Quinones from Cordia species from 1972 to 2023: isolation, structural diversity and pharmacological activities

Abstract Plants of the genus Cordia (Boraginaceae family) are widely distributed in the tropical regions of America, Africa, and Asia. They are extensively used in folk medicine due to their rich medicinal properties. This review presents a comprehensive analysis of the isolation, structure, biogenesis, and biological properties of quinones from Cordia species reported from 1972 to 2023. Meroterpenoids were identified as the major quinones in most Cordia species and are reported as a chemotaxonomic markers of the Cordia. In addition to this property, quinones are reported to display a wider and broader spectrum of activities, are efficient scaffold in biological activity, compared to other classes of compounds reported in Cordia, hence our focus on the study of quinones reported from Cordia species. About 70 types of quinones have been isolated, while others have been identified by phytochemical screening or gas chromatography. Although the biosynthesis of quinones from Cordia species is not yet fully understood, previous reports suggest that they may be derived from geranyl pyrophosphate and an aromatic precursor unit, followed by oxidative cyclization of the allylic methyl group. Studies have demonstrated that quinones from this genus exhibit antifungal, larvicidal, antileishmanial, anti-inflammatory, antibiofilm, antimycobacterial, antioxidant, antimalarial, neuroinhibitory, and hemolytic activities. In addition, they have been shown to exhibit remarkable cytotoxic effects against several cancer cell lines which is likely related to their ability to inhibit electron transport as well as oxidative phosphorylation, and generate reactive oxygen species (ROS). Their biological activities indicate potential utility in the development of new drugs, especially as active components in drug-carrier systems, against a broad spectrum of pathogens and ailments. Graphical Abstrac