Natural Products & Complementary Medicines: where are we up to?

The use of complementary and alternative medicine (CAM) has attracted much attention in recent years and has become a significant topic of debate within the healthcare sector. Many patients suffering from serious conditions such as cancer, Alzheimer’s disease, diabetes and lower back pain seek alternative therapies including CAM biological products. Clinicians and healthcare practitioners need to be aware of the available clinical evidence relating to CAM-based therapies when advising patients and recommending options. This review presents the recent clinical data investigating the efficacy of CAM therapies for disease management among these groups of patients. A number of cancer drugs are listed which have been developed from natural sources and which have recently gained approval from the EMA and FDA based on clinical trials. Reasons for using CAM and the most frequently used CAM therapies are mentioned as well as the degree of improvement of quality of life based on patients’ experiences

Bioguided isolation and pharmacological studies of cytotoxic principles from medicinal plants against malignant melanoma

Background and purpose: Malignant melanoma is the most aggressive form of skin cancer and natural products are an important source of anticancer lead compounds. The aim of this study is to search for agents with antimelanoma activity by studying 20 Saudi plants on human melanoma cells (A375). Methods: Bioguided isolation of active principles was performed utilising chromatographic methods and their characterisation was performed by NMR, MS and IR. Cell viability, proliferation and further mechanistic studies were conducted, including caspase-3/7, LDH, cell cycle analysis, AnnexinV/PI staining, cell morphology and Bax/Bcl-2 expression. Furthermore, the effect of drug combinations on melanoma migration was evaluated using B16-F10 cell lines in scratch and Transwell chamber assays. Results: Nine out of twenty plants showed significant cytotoxicity. Four cytotoxic lignans; justicidin A, justicidin B, tuberculatin and tuberculatin acetate were isolated from H. tuberculatum. They induced apoptosis due to the elevation of sub-G1 and AnnexinV positive populations and the activation of caspase-3/7. All lignans upregulated the Bax expression, but interestingly, justicidin A only downregulated the expression of Bcl-2 protein, suggesting the role of methyl substitution in this effect. Ursolic acid acetate, ursolic acid and quercetin were obtained from C. edulis. Ursolic acid acetate induced apoptosis (activating caspase-3/7, elevating AnnexinV positive population and Bax/Bcl-2 ratio), and caused cell cycle arrest at S phase. Morphological changes were stronger than those caused by ursolic acid, indicating that the acetyl group may potentiate the cytotoxicity. Combination studies showed synergistic antimigratory effects of ursolic acid and quercetin in melanoma migration at very low concentrations. Conclusion: This is the first time that cytotoxicity for most of the selected plants has been reported. This study sheds light on the mechanisms by which these extracts affect melanoma cells. Bioguided isolation did not afford new cytotoxic secondary metabolites, but allowed the study of the structure-activity relationship of important cytotoxic compounds like pentacyclic triterpenoids and arylnaphatalene lignans

Muslim pilgrims’ knowledge, attitudes, and practices regarding complementary and alternative medicine (CAM); a study conducted during Hajj season

Complementary and alternative medicine (CAM) has attracted much interest, and its prevalence in both developed and developing countries has increased. During the Hajj season, millions of Muslims from many different countries travel to Makkah for the pilgrimage. In dealing with health issues during the holy season, many pilgrims prefer to self-medicate with traditional remedies instead of visiting medical practitioners, which could affect the efforts of state healthcare organizations to maintain overall public health during this mass gathering. This study aims to gauge the prevalence of CAM use during Hajj, and to assess pilgrims’ beliefs and knowledge of CAM therapies, with particular reference to products available in Makkah. A cross-sectional survey was conducted in several camps and hotels occupied by Hajj pilgrims in Makkah, during Hajj 2023. CAM modalities were used by 68.8 % of the study participants during the Hajj season. There were almost equal numbers of men (53.7 %) and women (46.3 %) participants, with 88 % of the CAM users being non-Saudi and only 12 % Saudi. The majority of the CAM users belonged to two age groups, the 31–40 year group (29.9 %) and the 41–50 year group (34.5 %). The most frequent self-practice therapies were religious prayer/rituals (30.2 %), and the most popular practitioner therapies was herbal treatments (12.3 %). The most common source of CAM-related information was family/friends (29.2 %), for improving well-being reason (25.8 %). More than half of the participants (56.8 %) strongly believed that CAM therapies have the potential to cure disease, although they were unaware of possible interactions between CAM and conventional drugs (76.7 %). More than half of the participants (57.8 %) did not disclose their CAM usage to healthcare practitioners. Half of the sample said they used CAMs during Hajj because of the common belief that therapeutic products from the holy city of Makkah, such as Zamzam water, are more effective. In conclusion, CAM therapies are commonly used by Hajj pilgrims as they are presumed to be natural and therefore safe, raising concerns about the potential risks of relying on CAM without adequate consultation with healthcare providers or awareness of potential interactions between prescription drugs and CAM treatments

PLGA microparticles entrapping chitosan-based nanoparticles for the ocular delivery of ranibizumab

Age-related macular degeneration (AMD) is the leading cause of certified vision loss worldwide. The standard treatment for neovascular AMD involves repeated intravitreal injections of therapeutic proteins directed against vascular endothelial growth factor, such as ranibizumab. Biodegradable polymers, such as poly(lactic-co-glycolic acid) (PLGA), form delivery vehicles which can be used to treat posterior segment eye diseases, but suffer from poor protein loading and release. This work describes a “system-within-system”, PLGA microparticles incorporating chitosan-based nanoparticles, for improved loading and sustained intravitreal delivery of ranibizumab. Chitosan-N-acetyl-l-cysteine (CNAC) was synthesized and its synthesis confirmed using FT-IR and 1H NMR. Chitosan-based nanoparticles composed of CNAC, CNAC/tripolyphosphate (CNAC/TPP), chitosan, chitosan/TPP (chit/TPP), or chit/TPP-hyaluronic acid (chit/TPP-HA) were incorporated in PLGA microparticles using a modified w/o/w double emulsion method. Nanoparticles and final nanoparticles-within-microparticles were characterized for their protein–nanoparticle interaction, size, zeta potential, morphology, protein loading, stability, in vitro release, in vivo antiangiogenic activity, and effects on cell viability. The prepared nanoparticles were 17–350 nm in size and had zeta potentials of −1.4 to +12 mV. Microscopic imaging revealed spherical nanoparticles on the surface of PLGA microparticles for preparations containing chit/TPP, CNAC, and CNAC/TPP. Ranibizumab entrapment efficiency in the preparations varied between 13 and 69% and was highest for the PLGA microparticles containing CNAC nanoparticles. This preparation also showed the slowest release with no initial burst release compared to all other preparations. Incorporation of TPP to this formulation increased the rate of protein release and reduced entrapment efficiency. PLGA microparticles containing chit/TPP-HA showed the fastest and near-complete release of ranibizumab. All of the prepared empty particles showed no effect on cell viability up to a concentration of 12.5 mg/mL. Ranibizumab released from all preparations maintained its structural integrity and in vitro activity. The chit/TPP-HA preparation enhanced antiangiogenic activity and may provide a potential biocompatible platform for enhanced antiangiogenic activity in combination with ranibizumab. In conclusion, the PLGA microparticles containing CNAC nanoparticles showed significantly improved ranibizumab loading and release profile. This novel drug delivery system may have potential for improved intravitreal delivery of therapeutic proteins, thereby reducing the frequency, risk, and cost of burdensome intravitreal injections

Antibacterial and antibiofilm potentials of Rumex dentatus root extract characterized by HPLC-ESI-Q-TOF-MS

The control of infections is one of the key strategies to treat cuts, wounds, lung, and skin infections. In this study the folkloric use of Rumex dentatus (R. dentatus) roots in the mentioned conditions was scientifically investigated. The methanolic (MeOH) crude extract of R. dentatus root was fractionated (n-hexane, ethyl acetate and water) via bioassay-guided method, and its antibacterial activity was evaluated using the agar well diffusion and Minimum inhibitory concentration (MIC) assays against clinical isolate of Pseudomonas aeruginosa (P. aeruginosa). The antibiofilm activity was measured using the crystal violet staining method. The crude extract, fractions and sub-fractions tested showed the MICs values ranging from 200 to 1000 μg/mL respectively. Among the fractions, notably, the water fraction exhibited the highest activity against P. aeruginosa. The water fraction was then subjected to thin layer chromatography (TLC). Following spectrometric analysis using HPLC-ESI-Q-TOF-MS, gallic acid and emodin were identified as the primary components within the same fraction, responsible for eliciting antibacterial and antibiofilm effects. The in-silico studies conducted with AutoDock Vina on the LasR protein, using both isolated gallic acid and emodin, confirm the binding affinity of these molecules to the active sites of the LasR protein that has regulatory role in building of biofilm formation and its pathogenicity. By scientifically validating the infection-controlling properties of R. dentatus, this research provides compelling evidence that supports its traditional use as reported in folklore. Moreover, this study contributes to our understanding of the plant's potential in managing infections, thereby substantiating its traditional therapeutic application in a scientific context

Essential Oil Analysis and Antimicrobial Evaluation of Three Aromatic Plant Species Growing in Saudi Arabia

Arabian flora is a rich source of bioactive compounds. In this study, we investigated three aromatic plant species with the aim of finding valuable sources of antimicrobial agents against common pathogenic microorganisms. We focused especially on microorganisms, which cause outbreaks of infectious disease during mass gatherings and pilgrimages season in Saudi Arabia. The essential oils of three aromatic plant species were hydrodistilled from flowering aerial parts of Lavandula pubescens Decne. and Pulicaria incisa subsp. candolleana E.Gamal-Eldin, and from leaves, stems, ripe and unripe fruits of Juniperus procera Hochst. Ex Endl. They were subsequently analyzed by gas chromatography-mass spectrometry (GC-MS). The main constituents of L. pubescens were found to be carvacrol (55.7%), methyl carvacrol (13.4%), and beta-bisabolene (9.1%). P. incisa subsp. Candolleana essential oil was rich in linalool (33.0%), chrysanthenone (10.3%), eugenol (8.9%), and cis-chrysanthenol (8.0%); the major components of J. procera essential oil were alpha-pinene (31.3-62.5%) and delta-3-carene (7.3-30.3%). These essential oils were tested against thirteen American Type Culture Collection (ATCC) strains of Gram-positive and Gram-negative bacteria using the agar diffusion assay. The only effective essential oil was that of L. pubescens and the most sensitive strains were Acinetobacter baumannii, Salmonella typhimurium, Shigella sonnei, Enterococcus faecalis and Staphylococcus epidermidis. Carvacrol, the major constituent of L. pubescens, was tested on these strains and was compared with vancomycin, amikacin, and ciprofloxacin. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays of L. pubescens essential oil and carvacrol revealed that Gram-negative strains were more susceptible than the Gram-positive ones

Olive Leaf Extracts for a Green Synthesis of Silver-Functionalized Multi-Walled Carbon Nanotubes

Green biosynthesis, one of the most dependable and cost-effective methods for producing carbon nanotubes, was used to synthesize nonhazardous silver-functionalized multi-walled carbon nanotubes (SFMWCNTs) successfully. It has been shown that the water-soluble organic materials present in the olive oil plant play a vital role in converting silver ions into silver nanoparticles (Ag-NPs). Olive-leaf extracts contain medicinal properties and combining these extracts with Ag-NPs is often a viable option for enhancing drug delivery; thus, this possibility was employed for in vitro treating cancer cells as a proof of concept. In this study, the green technique for preparing SFMWCNTs composites using plant extracts was followed. This process yielded various compounds, the most important of which were Hydroxytyrosol, Tyrosol, and Oleuropein. Subsequently, a thin film was fabricated from the extract, resulting in a natural polymer. The obtained nanomaterials have an absorption peak of 419 nm in their UV–Vis. spectra. SEM and EDS were also used to investigate the SFMWCNT nanocomposites’ morphology simultaneously. Moreover, the MTT assay was used to evaluate the ability of SFMWCNTs to suppress cancer cell viability on different cancer cell lines, MCF7 (human breast adenocarcinoma), HepG2 (human hepatocellular carcinoma), and SW620 (human colorectal cancer). Using varying doses of SFMWCNT resulted in the most significant cell viability inhibition, indicating the good sensitivity of SFMWCNTs for treating cancer cells. It was found that performing olive-leaf extraction at a low temperature in an ice bath leads to superior results, and the developed SFMWCNT nanocomposites could be potential treatment options for in vitro cancer cells

Essential Oil Biodiversity of Achillea ligustica All. Obtained from Mainland and Island Populations

Background: The genus Achillea is rich in essential oil (EO) with high chemical diversity. In this study, eight EO samples obtained from flowers and leaves of Achillea ligustica All. collected on the Mediterranean mainland and island locations were analyzed to evaluate their possible chemical diversity. Methods: Sixteen samples of EO were analyzed by GC-MS, leading to the identification of 95 compounds in the leaves and 86 compounds in the flowers; a statistical analysis was performed to determine the chemical polymorphism. Results: Monoterpenes, such as β-pinene, borneol, α-terpineol and isobornyl acetate, were more abundant in the continental samples, while the insular samples were richer in 1,8-cineole. Fragranyl acetate and fragranol were detected in remarkable concentrations in sample 8. The fruits of sample 8 were then cultivated under controlled agronomic conditions, providing plants rich in these compounds (sample 9). The geographical variability influenced the EO compositions, with unique observed chemotypes and a high degree of diversity among samples collected in various areas (mainland or island). Statistical analyses did not reveal any pattern between the geographical provenience and the compositions. Conclusion: Samples were distributed based on the plant organ, confirming the already reported high degree of chemical polymorphism of this species. Sample 8 could be used as a source of fragranol and fragranyl acetate, with potential applications in the insecticidal and pheromone industries

Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine

Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to a rising interest in cancer therapy. However, this treatment method can lead to a deteriorating outcome of resistance, invasion, distant metastasis, and overall survival relative to its cytotoxicity. Furthermore, there are significant obstacles in tracking the efficacy of antiangiogenic treatments by incorporating positive biomarkers into clinical settings. These shortcomings underline the essential need to identify additional angiogenic inhibitors that target numerous angiogenic factors or to develop a new method for drug delivery of current inhibitors. The great benefits of nanoparticles are their potential, based on their specific properties, to be effective mechanisms that concentrate on the biological system and control various important functions. Among various therapeutic approaches, nanotechnology has emerged as a new strategy for treating different cancer types. This article attempts to demonstrate the huge potential for targeted nanoparticles and their molecular imaging applications. Notably, several nanoparticles have been developed and engineered to demonstrate antiangiogenic features. This nanomedicine could effectively treat a number of cancers using antiangiogenic therapies as an alternative approach. We also discuss the latest antiangiogenic and nanotherapeutic strategies and highlight tumor vessels and their microenvironments

Biological Screening of <i>Glycyrrhiza glabra</i> L. from Different Origins for Antidiabetic and Anticancer Activity

Background: Geographical variation may affect the phytochemistry as well as the biological activities of Glycyrrhiza glabra (licorice) root. Herein, a series of biological activities were performed to evaluate the impact of geographical origin on the biological potential of eight different licorice samples. Methodology: Cell culture studies were performed for cytotoxicity (MCF7, HCT116, HepG2, and MRC5), glucose uptake assay (HepG2), and glutathione peroxidase activity (HepG2), whereas α-amylase inhibition activity was tested for antidiabetic potential. Results: The Indian sample was observed to be more cytotoxic against MCF7 (22%) and HCT116 (43%) with an IC50 value of 56.10 (±2.38) μg/mL against the MCF7 cell line. The glucose uptake was seen with a mean value of 96 (±2.82) and a range of 92–101%. For glutathione peroxidase activity (GPx), the Syrian (0.31 ± 0.11) and Pakistani samples (0.21 ± 0.08) revealed a significant activity, whereas the Palestinian (70 ± 0.09) and Indian samples (68±0.06) effectively inhibited the α-amylase activity, with the lowest IC50 value (67.11 ± 0.97) μg/mL for the Palestinian sample. The statistical models of PCA (principal component analysis) and K-mean cluster analysis were performed to correlate the geographical origin, extract yield, and biological activities for the eight licorice samples of different origins. Conclusion: The licorice samples exhibited significant cytotoxic, GPx, and α-amylase inhibitory activity. The samples with higher extract yield showed more potential in these biological activities