Effect of Commiphora molmol on leukocytes proliferation in relation to histological alterations before and during healing from injury

Myrrh, Commiphora molmol has been used as anti-inflammatory and wound healing commercial product. Leukocyte count had been reliable indicator for clinicians to monitor progress of healing for their patients. We hypothesized that myrrh supplement participate in the activation of leukocyte proliferation pathway prior and post skin injury and gastric ulcer. The purpose of the present study was to examine long-term effect of myrrh on leukocytes proliferation before injury and during different stages of healing. Results showed that all types of leukocytes were significantly (p < 0.05) higher in the myrrh-treated groups before and during healing. The pretreatment with myrrh offered a time-dependent rise in leukocytes proliferation. Microscopic examination of blood smear from myrrh-treated rats with skin injury, showed an elevated count of middle-sized lymphocytes and neutrophils that were characterized with well-defined nuclear lobules and rich-granules cytoplasm. Furthermore, the microscopic examinations of the spleen and lymph nodes of myrrh-treated rats with skin injury, showed an increased thickness of lymphatic sheath around the arterioles in the white pulp that was associated with high density of the medium-sized lymphocytes in the secondary lymphoid follicles in the lymph nodes with engorged sinusoids. As myrrh enhanced leukocytes proliferation before injury, it can be concluded that myrrh posse’s antigenic-driven responses and that indicated some foreignness or toxicity of some constituents of myrrh. Because myrrh helped to maintain the relative rise of leukocytes counts throughout healing period and that implied it activated late steps of both proliferation and differentiation pathways for all types of leukocytes during effective phase of the specific immune responses.     

Hub genes identification and association of key pathways with hypoxia in cancer cells: A bioinformatics analysis

Three human cancer cell lines (A549, HCT116, and HeLa) were used to investigate the molecular mechanisms and potential prognostic biomarkers associated with hypoxia. We obtained gene expression data from Gene Expression Omnibus (GEO) datasets GSE11704, GSE147384, and GSE38061, which included 5 hypoxic and 8 control samples. Using the GEO2R tool and Venn diagram software, we identified common differentially expressed genes (cDEGs). The cDEGs were then subjected to Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway analysis by employing DAVID. The hub genes were identified from critical PPI subnetworks through CytoHuba plugin and these genes' prognostic significance and expression were verified using Kaplan-Meier analysis and Gene Expression Profiling Interactive Analysis (GEPIA), respectively. The research showed 676 common DEGs (cDEGs), with 207 upregulated and 469 downregulated genes. The STRING analysis showed 673 nodes and 1446 edges in the PPI network. We identified 4 significant modules and 19 downregulated hub genes. GO analysis revealed all of them were majorly involved in ribosomal large subunit assembly and biogenesis, rRNA processing, ribosome biogenesis, translation, RNA & protein binding frequently at the sites of nucleolus and nucleoplasm while 11 were significantly associated with a better prognosis of hypoxic tumors. Our research sheds light on the molecular mechanisms that underpin hypoxia in human cancer cell lines and identifies potential prognostic biomarkers for hypoxic tumors.     

CLIP-170S is a microtubule +TIP variant that confers resistance to taxanes by impairing drug-target engagement

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Herbal bioactivation, molecular targets and the toxicity relevance

There have been increasing reports on the adverse reactions associated with herbal consumption. For many of these adverse reactions, the underlying biochemical mechanisms are unknown, but bioactivation of herbal compounds to generate reactive intermediates have been implicated. This minireview updates our knowledge on metabolic activation of herbal compounds, molecular targets and the toxicity relevance. A number of studies have documented that some herbal compounds can be converted to toxic or even carcinogenic metabolites by Phase I [e.g. cytochrome P450s (CYPs)] and less frequently by Phase II enzymes. For example, aristolochic acids (AAs) in Aristolochia spp, which undergo reduction of the nitro group by hepatic CYP1A1/2 or peroxidases in extrahepatic tissues to generate highly reactive cyclic nitrenium ions. The latter can react with macromolecules (DNA and protein), resulting in activation of H-ras and myc oncogenes and gene mutation in renal cells and finally carcinogenesis of the kidneys. Teucrin A and teuchamaedryn A, two diterpenoids found in germander (Teuchrium chamaedrys) used as an adjuvant to slimming herbal supplements that caused severe hepatotoxicity, are converted by CYP3A4 to reactive epoxide which reacts with proteins such as CYP3A and epoxide hydrolase and inactivate them. Some naturally occurring alkenylbenzenes (e.g. safrole, methyleugenol and estragole) and flavonoids (e.g. quercetin) can undergo bioactivation by sequential 1-hydroxylation and sulfation, resulting in reactive intermediates capable of forming DNA adducts. Extensive pulegone metabolism generated p-cresol that is a glutathione depletory. The hepatotoxicity of kava is possibly due to intracellular glutathione depletion and/or quinone formation. Moreover, several herbal compounds including capsaicin from chili peppers, dially sulfone in garlic, methysticin and dihydromethysticin in kava, oleuropein in olive oil, and resveratrol found in grape seeds are mechanism-based (suicide) inhibitors of various CYPs. Together with advances of proteomics, metabolomics and toxicogenomics, an integrated systems toxicological approach may provide deep insights into mechanistic aspects of herb-induced toxicities, and contribute to bridging the relationships between herbal bioactivation, protein/DNA adduct formation and the toxicological consequences.     

The potential of South African plants in the development of new medicinal products

Southern Africa is an important focal point of botanical and cultural diversity but only a few plant species have hitherto become fully commercialised as medicinal products. In recent years there has been an upsurge in research and development activity, resulting in several new products and new crops. In this review, more than 90 of the best-known and most promising indigenous South African plants are listed and subjectively evaluated in the context of their potential for commercialisation as medicinal products for a variety of applications. The history of product development relating to the following species is briefly discussed and the plants and some of their products are illustrated: Agathosma betulina (buchu), Aloe ferox (bitter aloe), Artemisia afra (African wormwood), Aspalathus linearis (rooibos tea), Bulbine frutescens (burn jelly plant); Cyclopia genistoides (honeybush tea), Harpagophytum procumbens (devil's claw), Hoodia gordonii (hoodia, ghaap), Hypoxis hemerocallidea (“African potato”), Lippia javanica (fever tea), Mesembryanthemum tortuosum (= Sceletium tortuosum) (kanna, kougoed), Pelargonium sidoides (“Umckaloabo”), Siphonochilus aethiopicus (African ginger), Sutherlandia frutescens (= Lessertia frutescens) (cancer bush), Warburgia salutaris (pepperbark tree) and Xysmalobium undulatum (“Uzara”). The main factors that are apparently responsible for failure or success will be highlighted, especially the importance of marketing strategy, proof of concept and barriers to market entry.     

Honeybush (Cyclopia spp.): From local cottage industry to global markets — The catalytic and supporting role of research

Honeybush tea (Cyclopia spp.), one of the traditional South African herbal teas with a long history of regional use, remained a cottage industry until the mid-1990s when researchers were instrumental in the development of a formal agricultural and agro-processing industry. It is one of the few indigenous South African plants that made the transition from the wild to a commercial product during the past 100 years. Research activities during the past 20 years included propagation, production, genetic improvement, processing, composition and the potential for value-adding. The present review provides an up-to-date and comprehensive record of the development of the South African honeybush industry, against the background of the historical highlights in the making of an industry. It provides a blueprint of the processes and actions involved in the development of a new agricultural and agro-processing industry from an herbal plant. Insight into challenges faced by the industry and future research needed to keep it competitive are provided.     

Effects of Echinaforce treatment on ex vivo-stimulated blood cells

The herb Echinacea purpurea, also called purple coneflower, is regarded as an immune modulator. This study examined changes in cytokine production in blood samples from 30 volunteers before and during 8-day oral administration with an ethanolic extract of fresh Echinacea purpurea (Echinaforce^®). Daily blood samples were ex vivo stimulated by LPS/SEB or Zymosan and analysed for a series of cytokines and haematological and metabolic parameters. Treatment reduced the proinflammatory mediators TNF-α and IL-1β by up to 24% (p < 0.05) and increased anti-inflammatory IL-10 levels by 13% (p < 0.05) in comparison to baseline. This demonstrated a substantial overall anti-inflammatory effect of Echinaforce^® for the whole group (n = 28). Chemokines MCP-1 and IL-8 were upregulated by 15% in samples from subjects treated with Echinaforce^® (p < 0.05). An analysis of a subgroup of volunteers who showed low pre-treatment levels of the cytokines MCP-1, IL-8, IL-10 or IFN-γ (n = 8) showed significant stimulation of these factors upon Echinaforce^® treatment (30-49% increases; p < 0.05), whereas the levels in subjects with higher pre-treatment levels remained unaffected. We chose the term “adapted immune-modulation” to describe this observation. Volunteers who reported high stress levels (n = 7) and more than 2 colds per year experienced a significant transient increase in IFN-γ upon Echinaforce^® treatment (>50%). Subjects with low cortisol levels (n = 11) showed significant down-regulation of the acute-phase proteins IL1-β, IL-6, IL-12 and TNF-α by Echinaforce^® (range, 13-25%), while subjects with higher cortisol levels showed no such down-regulation. This is the first ex vivo study to demonstrate adapted immune-modulation by an Echinacea preparation. While Echinaforce^® did not affect leukocyte counts, we speculate that the underlying therapeutic mechanism is based on differential multi-level modulation of the responses of the different types of leukocytes. Echinaforce^® thus regulates the production of chemokines and cytokines according to current immune status, such as responsiveness to exogenous stimuli, susceptibility to viral infection and exposure to stress.     

Leishmania donovani: assessment of leishmanicidal effects of herbal extracts obtained from plants in the visceral leishmaniasis endemic area of Bihar, India

One obstacle faced in the effective control of visceral leishmaniasis (VL) is the limited number of available treatment options. Furthermore, control efforts have been hindered further by the emergence of Leishmania resistance to many of the available drugs. In this study, we investigated the anti-leishmanial properties of 30 medicinally important plants from the VL endemic area of Bihar, India and compared them to two available anti-leishmanial drugs (sodium antimony gluconate and amphotericin B) and two plant lectins (phytohemagglutinin and concanavalin A) on Leishmania donovani promastigotes in vitro at 24 and 48 h after initiation of culture. We identified eight plant extracts in addition to phytohemagglutinin and amphotericin B that significantly inhibited the growth of promastigotes (p < 0.03). We further studied the minimum effective concentrations as well as the effect on axenic amastigotes viability and the cell cytotoxicity on human peripheral blood of four (Agave americana, Azadirachta indica, Eclipta alba and Piper longum) of the eight plant extracts that induced significant promastigotes killing (p = 0.00098). Effect-based dose finding analysis revealed that the threshold concentration of A. americana required to eliminate L. donovani after 24 h was 0.05 mg/ml. A. indica and P. longum plant extracts eliminated L. donovani promastigotes after 48 h at concentrations of 0.1 and 0.5 mg/ml, respectively. E. alba eliminated the promastigotes at a concentration of 0.5 mg/ml within 24 h. The axenic amastigote killing response was 1.90-, 2.52- and 1.3-fold higher than the promastigote killing response with A. indica, A. americana and E. alba plant extracts, respectively. A. americana and A. indica, respectively, led to approximate 2.5- and 1.3-fold declines in mitochondrial dehydrogenase activity compared with control. E. alba stimulation resulted in an up-regulation of dehydrogenase activity (p = 0.00329). The CSA from P. longum was found to be least cytotoxic; the observed difference in mitochondrial activity was insignificant (p = 0.16314). Further studies may reveal the pharmacological significance of many of the plants with anti-leishmanial properties identified in the present study.