Differential Anti-Fibrotic and Remodeling Responses of Human Dermal Fibroblasts to Artemisia sp., Artemisinin, and Its Derivatives.

Fibrosis is a ubiquitous pathology, and prior studies have indicated that various artemisinin (ART) derivatives (including artesunate (AS), artemether (AM), and dihydroartemisinin (DHA)) can reduce fibrosis in vitro and in vivo. The medicinal plant Artemisia annua L. is the natural source of ART and is widely used, especially in underdeveloped countries, to treat a variety of diseases including malaria. A. afra contains no ART but is also antimalarial. Using human dermal fibroblasts (CRL-2097), we compared the effects of A. annua and A. afra tea infusions, ART, AS, AM, DHA, and a liver metabolite of ART, deoxyART (dART), on fibroblast viability and expression of key fibrotic marker genes after 1 and 4 days of treatment. AS, DHA, and Artemisia teas reduced fibroblast viability 4 d post-treatment in up to 80% of their respective controls. After 4 d of treatment, AS DHA and Artemisia teas downregulated ACTA2 up to 10 fold while ART had no significant effect, and AM increased viability by 10%. MMP1 and MMP3 were upregulated by AS, 17.5 and 32.6 fold, respectively, and by DHA, 8 and 51.8 fold, respectively. ART had no effect, but A. annua and A. afra teas increased MMP3 5 and 16-fold, respectively. Although A. afra tea increased COL3A1 5 fold, MMP1 decreased >7 fold with no change in either transcript by A. annua tea. Although A. annua contains ART, it had a significantly greater anti-fibrotic effect than ART alone but was less effective than A. afra. Immunofluorescent staining for smooth-muscle α-actin (α-SMA) correlated well with the transcriptional responses of drug-treated fibroblasts. Together, proliferation, qPCR, and immunofluorescence results show that treatment with ART, AS, DHA, and the two Artemisia teas yield differing responses, including those related to fibrosis, in human dermal fibroblasts, with evidence also of remodeling of fibrotic ECM.

Microenvironment created by Plantago lagopus L. may affect cover and diversity of coexisting species in urban vegetation.

Some plant species may exhibit new microenvironments which lead to significant changes in the cover and diversity of the coexisting species. In this investigation, we evaluated the effects of Plantago lagopus L. on the cover and diversity of the associated plant species in the urban vegetation. A total of 70 plots were conducted in sites with- and without this species in urban gardens. Cover of the associated species and different diversity indices including species richness, Shannon-Wiener, evenness, and Simpson indices were measured. The allelopathic potential of P. lagopus was verified using its rhizosphere and non-rhizosphere soils on two target species existing within the same environment. Some soil criteria and seed sizes of the associated species were also determined. Most of the coexisting weeds were reduced in terms of their cover in plots with Plantago. The reduction of plant diversity depended on its cover. Besides, the aboveground biomass was reduced in sites comprising Plantago. The degree of inhibition was not related to the seed size of the species found. This species reduced the incident solar radiation and the local temperature over the soil surface. The locations exhibiting such species contained lower contents of available potassium and zinc. Rhizosphere soil of P. lagopus substantially inhibited germination and growth of Amaranthus viridis, but it didn't do so for Medicago lupulina. Reduction in cover, diversity, and biomass of the urban weeds associated with P. lagopus may be related to the reduction of received solar radiation, soil temperature, and nutrient availability. The allelopathic potential of P. lagopus may have a partial role in this reduction. These results suggest that P. lagopus may create a microenvironment of new conditions not favorable for most of the coexisting species.

Endophytic Aspergillus hiratsukae mediated biosynthesis of silver nanoparticles and their antimicrobial and photocatalytic activities.

In the current study, endophytic Aspergillus hiratsukae was used for the biosynthesis of silver nanoparticles (Ag-NPs) for the first time. The characterizations were performed using X ray diffraction (XRD), Transmission electron microscopy (TEM), Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX), Dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectroscopy. The obtained results demonstrated the successful formation of crystalline, spherical Ag-NPs with particle diameters ranging from 16 to 31 nm. The FT-IR studied and displayed the various functional groups involved, which played a role in capping and reducing agents for Ag-NPs production. The SEM-EDX revealed that the main constituent of the AS-formed sample was primarily Ag, with a weight percentage of 64.2%. The mycosynthesized Ag-NPs were assessed for antimicrobial as well as photocatalytic activities. The antimicrobial results indicated that the synthesized Ag-NPs possess notable antibacterial efficacy against Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, with minimum inhibitory concentrations (MICs) of Ag-NPs ranging from 62.5 to 250 µg/mL. Moreover, the biosynthesized Ag-NPs demonstrated weak antifungal activity against Aspergillus brasiliensis and Candida albicans, with MICs of 500 and 1,000 µg/mL, respectively. In addition, the mycosynthesized Ag-NPs exhibited photocatalytic activity toward acid black 2 (nigrosine) dye under both light and dark stimulation. Notably, After 300 min exposure to light, the nigrosine dye was degraded by 93%. In contrast, 51% degradation was observed after 300 min in darkness. In conclusion, Ag-NPs were successfully biosynthesized using endophytic A. hiratsukae and also exhibited antimicrobial and photocatalytic activities that can be used in environmental applications.

Biocontrol of Rice Seed-Associated Fungal Pathogens Using Green Synthesis Approaches.

Rice (Oryza sativa) is a major cereal crop that balances the food demand of the worldwide population. The crop quality drops daily due to their exposure to biotic and abiotic stresses, especially pathogens. It needs to be improved to maintain the consumption level to cope with increasing population demands for food. The current study was designed to analyze the comparison of the effects of green synthesis approaches on pathogens associated with rice seeds. In this study, essential oils were extracted from Cymbopogon citratus, Thymus vulgaris, and Origanum vulgaris medicinal plants and used as fungicides on fungal strains of Aspergillus spp. T. vulgaris effectively controlled the growth of Aspergillus niger, Aspergillus flavus, and Aspergillus terreus as compared with O. vulgaris and Cymbopogon. Further, silica nanoparticles (SiNPs) were synthesized from rice husk to evaluate their antifungal activities. SiNPs were characterized by ultraviolet-visible spectroscopy with a broad peak at 281.62 nm. Fourier-transform infrared spectroscopy spectrum confirms the presence of Si-H, Si-OH, and Si-O-Si bonds functional groups, and SiO4 tetrahedral coordination unit. X-ray diffraction pattern describes the crystalline structure with a sharp peak at 2θ = 22°. Scanning electron microscopy and energy-dispersive spectroscopy confirmed the spherical shape, size 70-115 nm, and elemental composition with pure silica contents. SiNPs showed no significant antifungal activity against Aspergillus strains. Moreover, Trichoderma was isolated from the rhizosphere of rice fields and showed a surprising antifungal effect against A. terreus, A. niger, and A. flavus. The current study successfully revealed environment-friendly and cost-effective green synthesizing approaches for analyzing biocontrol potential against rice seed-related Aspergillus spp. They will also help to improve pathogen control strategies in other cereals.

Dense Cover, but Not Allelopathic Potential, of Naturalized Alien Cenchrus echinatus L. Threatens the Native Species in Urban Vegetation.

Exotic plants usually exhibit problems for native species where they coexist. This study evaluated the effect of naturalized alien Cenchrus echinatus L. on native plants in urban vegetation. A field trial was conducted to assess the effect of this species on the cover and diversity of the native vegetation. The allelopathic potential of such species was examined. Sites comprising C. echinatus had a lower cover than some native species. Lower floristic diversity was observed at higher densities of this plant. The soil under this plant attained lower N, P, and K contents. This soil had no effect on the germination and growth of native species. It also comprised germinable seeds of some species which were absent from the standing vegetation. Exotic C. echinatus may exert negative effects on the native vegetation of the urban plant communities. A dense cover of this species may inhibit the germination of native species, leading to a reduction in their cover. Reduction in cover and diversity of native species may not be attributed to allelopathy. These results suggest that naturalized C. echinatus may be more competitive than the native ones, particularly at higher densities. Furthermore, it may represent a threat to the native plants in the urban vegetation.

Evaluation of Biogenic Silver Nanoparticles Synthesized from Vegetable Waste.

Introduction: Vegetable waste has numerous essential values and can be used for various purposes. Unfortunately, it is often discarded worldwide due to a lack of awareness regarding its nutritional and practical significance. Even the nutrient-rich peels of fruits and vegetables are commonly wasted, despite their numerous useful applications. Utilizing vegetable waste to produce silver nanoparticles through green synthesis is an advantageous, economical, and environmentally friendly method for producing valuable products while addressing waste management concerns. The main emphasis of this study was to synthesize silver nanoparticles (AgNPs) by using vegetable waste from Solanum tuberosum (potato) and Coriander sativum (coriander). Methods: The stems of Coriander sativum and peels of Solanum tuberosum were used as extracts for the synthesis of AgNPs. The characterization of the synthesized AgNPs involved UV-spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The phytochemical analysis was performed to analyze antimicrobial, cytotoxic, antidiabetic, antitumor, antioxidant, alpha-amylase, and protein inhibition activities. Results: The change in the color of the reaction mixture from yellowish green to brown following the addition of extracts to the silver nitrate solution confirmed nanoparticle synthesis. UV analysis has shown peaks in the range of 300-400nm. SEM confirmed the spherical and agglomerated morphology and size of 64nm for potato peel and 70nm for coriander stem. XRD confirmed the crystalline structure of silver nanoparticles. The phytochemical assays confirmed that silver nanoparticles had higher total phenolic and flavonoid contents. The biosynthesized silver nanoparticles showed promising antimicrobial, cytotoxic, antidiabetic, antitumor, and antioxidant properties and significant alpha-amylase and protein inhibition activities in comparison with the crude extracts. Conclusion: The bioactivity of the plant suggests that it could be a suitable option for therapeutic purposes. This study demonstrates a potential method for sustainable nanoparticle synthesis and the therapeutic applications of AgNPs derived from vegetable waste. By utilizing the potential of vegetable waste, we can contribute to both environmental sustainability and the development of innovative, valuable products in fields such as medicine, agriculture, and materials science. These findings encourage further research on agricultural byproducts, promoting environmentally friendly and economically advantageous research and development efforts.

Artemisia afra and Artemisia annua Extracts Have Bactericidal Activity against Mycobacterium tuberculosis in Physiologically Relevant Carbon Sources and Hypoxia.

Mycobacterium tuberculosis (Mtb) is a deadly pathogen and causative agent of human tuberculosis, causing ~1.5 million deaths every year. The increasing drug resistance of this pathogen necessitates novel and improved treatment strategies. A crucial aspect of the host-pathogen interaction is bacterial nutrition. In this study, Artemisia annua and Artemisia afra dichloromethane extracts were tested for bactericidal activity against Mtb strain mc26230 under hypoxia and various infection-associated carbon sources (glycerol, glucose, and cholesterol). Both extracts showed significant bactericidal activity against Mtb, regardless of carbon source. Based on killing curves, A. afra showed the most consistent bactericidal activity against Mtb for all tested carbon sources, whereas A. annua showed the highest bactericidal activity in 7H9 minimal media with glycerol. Both extracts retained their bactericidal activity against Mtb under hypoxic conditions. Further investigations are required to determine the mechanism of action of these extracts and identify their active constituent compounds.

Biogenic Synthesis of Zinc Oxide Nanoparticles Using Citrullus colocynthis for Potential Biomedical Applications.

Green nanoparticle synthesis is considered the most efficient and safe nanoparticle synthesis method, both economically and environmentally. The current research was focused on synthesizing zinc oxide nanoparticles (ZnONPs) from fruit and leaf extracts of Citrullus colocynthis. Four solvents (n-hexane, methanol, ethyl acetate, and aqueous) were used to prepare the extracts from both plant parts by maceration and extraction. Zinc acetate was used to synthesize the nanoparticles (NPs), and color change indicated the synthesis of ZnONPs. X-ray diffraction, UV spectroscopy, and scanning electron microscopy were used to study the ZnONPs. UV-visible spectroscopy revealed an absorbance peak in the 350-400 nm range. XRD patterns revealed the face-centered cubic structure of the ZnONPs. SEM confirmed a spherical morphology and a size range between 64 and 82 nm. Phytochemical assays confirmed that the complete flavonoid, phenolic, and alkaloid concentrations were higher in unrefined solvent extracts than in nanoparticles. Nanoparticles of C. colocynthis fruit aqueous extracts showed stronger antioxidant activity compared with the crude extracts. Strong antifungal activity was exhibited by the leaves, crude extracts, and nanoparticles of the n-hexane solvent. In a protein kinase inhibition assay, the maximum bald zone was revealed by nanoparticles of ethyl acetate extracts from leaves. The crude extracts and nanoparticles of leaves showed high cytotoxic activities of the n-hexane solvent, with LC50 values of 42.08 and 46.35, respectively. Potential antidiabetic activity was shown by the n-hexane (93.42%) and aqueous (82.54%) nanoparticles of the fruit. The bioactivity of the plant showed that it is a good candidate for therapeutic use. The biosynthesized ZnONPs showed promising antimicrobial, cytotoxic, antidiabetic, and antioxidant properties. Additionally, the in vivo assessment of a nano-directed drug delivery system for future therapeutic use can be conducted based on this study.

Comparative evaluation of biomedical and phytochemical applications of zinc nanoparticles by using Fagonia cretica extracts.

The use of the green approach for nanoparticle synthesis yielded noticeable concern due to its eco-friendliness, cost-effectiveness, and reduced production of toxic chemicals. The current study was designed to formulate Zinc oxide nanoparticles (ZnO NPs) by using Fagonia cretica extracts, evaluating its phytochemical content, and different biological activities. Four different solvents; methanol (MeOH), n-Hexane (n-H), aqueous (Aq), and ethyl acetate (EA), had been utilized in the extracting method. ZnO NPs were successfully synthesized and characterized by UV-vis spectroscopy and scanning electron microscopy (SEM). The UV-vis spectra showed absorbance peaks between 350-400 nm range and SEM analysis revealed spherical morphology with particle sizes ranging from 65-80 nm. In phytochemical analysis, crude extracts exhibited the highest phytochemical content as they contain enriched secondary metabolites. n-hexane extract showed the highest phenolic contents while aqueous extracts showed the highest flavonoid content. Maximum free radicle scavenging activity was observed in NPs synthesized from ethyl-acetate extract with an IC50 value of 35.10 µg/ml. Significant antibacterial activity was exhibited by NPs polar solvents against K. pneumonae, E. coli, and B. subtilis. Polar solvents showed considerable antifungal potential against A. flavus and F. solani. NPs synthesized from nH extract showed potential cytotoxic activity with an LC50 value of 42.41 µg/ml against brine shrimps. A noteworthy antidiabetic activity was exhibited by nanoparticles synthesized from methanol extract i.e., 52.61 ± 0.36%. Significant bald zones were observed in nanoparticles synthesized from methanol extract rendering protein kinase inhibition. The present study highlights the significance of F. indica as a natural source for synthesizing functional nanoparticles with substantial antioxidant, antimicrobial, cytotoxic, protein kinase inhibitory, and antidiabetic properties.

Comparative Evaluation of Biomedical Applications of Zinc Nanoparticles Synthesized by Using Withania somnifera Plant Extracts.

Green synthesis of metal nanoparticles is of great importance in the modern health care system. In this study, zinc nanoparticles (ZnONPs) were synthesized using leaf and root extracts of Withania somnifera using four different solvents. ZnONPs were characterized by UV-vis spectrophotometer with a range between 350-400 nm. Scanning electron microscope revealed spherical morphology with an overall size of 70-90 nm and XRD pattern confirmed the crystalline structure. The total flavonoids, phenolic, and alkaloid contents were significantly greater in the crude extracts as compared to ZnONPs. The highest scavenging activity was observed in ZnONPs from n-hexane and ethyl-acetate extracts of roots with IC50 values of 27.36 µg/mL and 39.44 µg/mL, respectively. ZnONPs from methanol and aqueous extracts showed significant antibacterial activity against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis while none of the extracts were found to have significant antifungal activity. Maximum cytotoxic activity was observed in ZnONPs synthesized from aqueous and n-hexane root extracts with LC50 values of 9.36 µg/mL and 18.84 µg/mL, respectively. The highest antidiabetic potential was exhibited by ZnONPs from n-hexane leaf extracts, i.e., 47.67 ± 0.25%. Maximum protein kinase inhibitory potential was observed in ZnONPs of ethyl-acetate extract of roots with a bald zone of 12 mm. These results indicated that Withania somnifera-based ZnONPs showed significant biological activities compared to crude extracts. These findings can further be utilized for in-vivo analysis of nano-directed drug delivery systems.

Immunoinformatics approaches to explore B and T cell epitope-based vaccine designing for SARS-CoV-2 Virus.

SARS-CoV-2, a new world coronavirus belonging to class Nidovirales of Coronaviridae family causes COVID-19 infection which is the leading cause of death worldwide. Currently there are no approved drugs and vaccines available for the prevention of COVID-19 infection, although couples of immunizations are being tested in clinical trials. However, the present efforts are focused on computational vaccination technique for evaluating candidates to design multi-epitope-based vaccine against pathogenic mechanism of novel SARS-COV-2. Based on recent published evidence, we recognized spike glycoprotein and envelope small membrane protein are the potential targets to combat the pathogenic mechanism of SARS-CoV-2. Similarly, in the present study we identified epitope of both B and T cell associated with these proteins. Extremely antigenic, conserve, immunogenic and nontoxic epitope of B and T cell of Spike protein are WPWYVWLGFI, SRVKNLNSSEGVPDLLV whereas the CWCARPTCIK and YCCNIVNVSL are associated with envelope small membrane protein were selected as potential candidate for vaccine designing. These epitopes show virtuous interaction with HLAA0201 during molecular docking analysis. Under simulation protocol the predicted vaccine candidates show stability. Collectively, this work provides novel potential candidates for epitope-based vaccine designing against COVID-19 infection.

Artemisinin and its derivatives: a promising cancer therapy.

The world is experiencing a cancer epidemic and an increase in the prevalence of the disease. Cancer remains a major killer, accounting for more than half a million deaths annually. There is a wide range of natural products that have the potential to treat this disease. One of these products is artemisinin; a natural product from Artemisia plant. The Nobel Prize for Medicine was awarded in 2015 for the discovery of artemisinin in recognition of the drug's efficacy. Artemisinin produces highly reactive free radicals by the breakdown of two oxygen atoms that kill cancerous cells. These cells sequester iron and accumulate as much as 1000 times in comparison with normal cells. Generally, chemotherapy is toxic to both cancerous cells and normal cells, while no significant cytotoxicity from artemisinin to normal cells has been found in more than 4000 case studies, which makes it far different than conventional chemotherapy. The pleiotropic response of artemisinin in cancer cells is responsible for growth inhibition by multiple ways including inhibition of angiogenesis, apoptosis, cell cycle arrest, disruption of cell migration, and modulation of nuclear receptor responsiveness. It is very encouraging that artemisinin and its derivatives are anticipated to be a novel class of broad-spectrum antitumor agents based on efficacy and safety. This review aims to highlight these achievements and propose potential strategies to develop artemisinin and its derivatives as a new class of cancer therapeutic agents.

Self-Redirection of Metabolic Flux Toward Squalene and Ethanol Pathways by Engineered Yeast.

We have previously reported that squalene overproducing yeast self-downregulate the expression of the ethanol pathway (non-essential pathway) to divert the metabolic flux to the squalene pathway. In this study, the effect of co-production of squalene and ethanol on other non-essential pathways (fusel alcohol pathway, FA) of Saccharomyces cerevisiae was evaluated. However, before that, 13 constitutive promoters, like IRA1p, PET9p, RHO1p, CMD1p, ATP16p, USA3p, RER2p, COQ1p, RIM1p, GRS1p, MAK5p, and BRN1p, were engineered using transcription factor bindings sites from strong promoters HHF2p (-300 to -669 bp) and TEF1p (-300 to -579 bp), and employed to co-overexpress squalene and ethanol pathways in S. cerevisiae. The FSE strain overexpressing the key genes of the squalene pathway accumulated 56.20 mg/L squalene, a 16.43-fold higher than wild type strain (WS). The biogenesis of lipid droplets was stimulated by overexpressing DGA1 and produced 106 mg/L squalene in the FSE strain. AFT1p and CTR1p repressible promoters were also characterized and employed to downregulate the expression of ERG1, which also enhanced the production of squalene in FSE strain up to 42.85- (148.67 mg/L) and 73.49-fold (255.11 mg/L) respectively. The FSE strain was further engineered by overexpressing the key genes of the ethanol pathway and produced 40.2 mg/mL ethanol in the FSE1 strain, 3.23-fold higher than the WS strain. The FSE1 strain also self-downregulated the expression of the FA pathway up to 73.9%, perhaps by downregulating the expression of GCN4 by 2.24-fold. We demonstrate the successful tuning of the strength of yeast promoters and highest coproduction of squalene and ethanol in yeast, and present GCN4 as a novel metabolic regulator that can be manipulated to divert the metabolic flux from the non-essential pathway to engineered pathways.

Biotechnological approaches for artemisinin production in Artemisia.

Artemisinin and its analogues are naturally occurring most effective antimalarial secondary metabolites. These compounds also possess activity against various types of cancer cells, schistosomiasis, and some viral diseases. Artemisinin and its derivatives (A&D) are found in very low amounts in the only natural source i.e. Artemisia plant. To meet the global needs, plant sources have been exploited for the enhanced production of these natural products because their chemical synthesis is not profitable. The generally adopted approaches include non-transgenic (tissue and cell cultures) and transgenic together with the cell, tissue, and whole transgenic plant cultures. The genes targeted for the overproduction of A&D include the biosynthetic pathway genes, trichome development genes and rol genes, etc. Artemisinin is naturally produced in trichomes of leaves. At the same time, transgenic hairy roots are considered a good source to harvest artemisinin. However, the absence of trichomes in hairy roots suggests that artemisinin biosynthesis is not limited to trichomes. Moreover, the expression of the gene involved in trichome development and sesquiterpenoid biosynthesis (TFAR1) in transgenic and non-transgenic roots provokes researchers to look for new insight of artemisinin biosynthesis. Here we discuss and review precisely the various biotechnological approaches for the enhanced biosynthesis of A&D.

Cellular engineering of Artemisia annua and Artemisia dubia with the rol ABC genes for enhanced production of potent anti-malarial drug artemisinin.

BACKGROUND: Malaria is causing more than half of a million deaths and 214 million clinical cases annually. Despite tremendous efforts for the control of malaria, the global morbidity and mortality have not been significantly changed in the last 50 years. Artemisinin, extracted from the medicinal plant Artemisia sp. is an effective anti-malarial drug. In 2015, elucidation of the effectiveness of artemisinin as a potent anti-malarial drug was acknowledged with a Nobel prize. Owing to the tight market and low yield of artemisinin, an economical way to increase its production is to increase its content in Artemisia sp. through different biotechnological approaches including genetic transformation. METHODS: Artemisia annua and Artemisia dubia were transformed with rol ABC genes through Agrobacterium tumefacienes and Agrobacterium rhizogenes methods. The artemisinin content was analysed and compared between transformed and untransformed plants with the help of LC-MS/MS. Expression of key genes [Cytochrome P450 (CYP71AV1), aldehyde dehydrogenase 1 (ALDH1), amorpha-4, 11 diene synthase (ADS)] in the biosynthetic pathway of artemisinin and gene for trichome development and sesquiterpenoid biosynthetic (TFAR1) were measured using Quantitative real time PCR (qRT-PCR). Trichome density was analysed using confocal microscope. RESULTS: Artemisinin content was significantly increased in transformed material of both Artemisia species when compared to un-transformed plants. The artemisinin content within leaves of transformed lines was increased by a factor of nine, indicating that the plant is capable of synthesizing much higher amounts than has been achieved so far through traditional breeding. Expression of all artemisinin biosynthesis genes was significantly increased, although variation between the genes was observed. CYP71AV1 and ALDH1 expression levels were higher than that of ADS. Levels of the TFAR1 expression were also increased in all transgenic lines. Trichome density was also significantly increased in the leaves of transformed plants, but no trichomes were found in control roots or transformed roots. The detection of significantly raised levels of expression of the genes involved in artemisinin biosynthesis in transformed roots correlated with the production of significant amounts of artemisinin in these tissues. This suggests that synthesis is occurring in tissues other than the trichomes, which contradicts previous theories. CONCLUSION: Transformation of Artemisia sp. with rol ABC genes can lead to the increased production of artemisinin, which will help to meet the increasing demand of artemisinin because of its diverse pharmacological and anti-malarial importance.