A Comparative Study on the Antidiabetic Activity, Cytotoxicity and Lipid Profile of Trichilia emetica Oils.

The Trichilia emetica plant is traditionally used for medicinal and food purposes. However, there are limited studies on the bioactivity and cytotoxicity of its seed butter and aril oil. This study aimed to assess the antidiabetic activity and cytotoxicity of seed butter and aril oil, obtained via two different extraction methods, and compare their lipid profiles. The plant samples were collected from the Faifa mountains and extracted using a Soxhlet apparatus for hot extraction and a magnetic stirrer for cold maceration. The antidiabetic activity and cytotoxicity were evaluated using the α-amylase and MTT assays, respectively. The fatty acids were quantified utilizing gas chromatography-mass spectrometry. This study proves the impact of the extraction method on the yield, cytotoxicity, antidiabetic activity and lipid profile. The highest cytotoxicity was observed with the seed butter obtained via Soxhlet extraction. The α-amylase inhibition was observed at the highest levels with the seed butter and aril oil obtained via cold maceration. The palmitic acid (PA) and oleic acid (OA) were detected at their maximal concentrations in the seed butter obtained via Soxhlet extraction and aril oil obtained via cold maceration, respectively. This study represents an essential basis for understanding the importance of T. emetica as a valuable tree for food, cosmetic and medicinal purposes. Further experiments can lead to the development of green extraction techniques and isolation of the cytotoxic and antidiabetic molecules that can be developed into new pharmaceutical products or serve as lead molecules for new drugs.

Natural products as promising modulators of breast cancer immunotherapy.

Breast cancer (BC) is the most common malignancy among women and is considered a major global health challenge worldwide due to its high incidence and mortality rates. Treatment strategies for BC is wide-ranging and include surgery, radiotherapy, chemotherapy, targeted hormonal therapy and immunotherapy. Immunotherapy has gained popularity recently and is often integrated as a component of personalized cancer care because it aims to strengthen the immune system and enable it to recognize and eradicate transformed cells. It has fewer side-effects and lower toxicity than other treatment strategies, such as chemotherapy. Many natural products are being investigated for a wide range of therapeutic pharmacological properties, such as immune system modulation and activity against infection, auto-immune disease, and cancer. This review presents an overview of the major immune response-related pathways in BC, followed by detailed explanation of how natural compounds can act as immunomodulatory agents against biomolecular targets. Research has been carried out on many forms of natural products, including extracts, isolated entities, synthetic derivatives, nanoparticles, and combinations of natural compounds. Findings have shown significant regulatory effects on immune cells and immune cytokines that lead to immunogenic cancer cell death, as well as upregulation of macrophages and CD+8 T cells, and increased natural killer cell and dendritic cell activity. Natural products have also been found to inhibit some immuno-suppressive cells such as Treg and myeloid-derived suppressor cells, and to decrease immunosuppressive factors such as TGF-ß and IL-10. Also, some natural compounds have been found to target and hinder immune checkpoints such as PD-L1.

A comprehensive LCMS/MS characterization for the green extracted cucurbitane-triterpenoid glycosides from bitter melon (Momordica charantia) fruit.

A first-time green extraction and LCMSMS analysis for karavilosides (KVs) VIII, X, and XI in different parts (skin, pith, and seed) of the fresh and dried fruit of bitter melon (BM) is reported herein. Ultrasonication for green extraction whereas, LCMS/MS for KVs quantification were used. More extract yield (675.80 ± 163.57 mg/g) was observed for the dried fruit parts compared to the fresh BM-fruit parts (513.20 ± 75.42 mg/g). The fresh skin (343.40 ± 54.07 mg/4g) and dried seeds (311.80 and 77.95 ± 38.98) exhibited more yield whereas, the solvent yield (mg/4mg) observed was; H2O (651.70) > EtOH (227.20) > EtAC (163.30) > ACT (146.80). The LCMS/MS yield for the KVs revealed a descending order; KVXI (2376.44 ppb) > KVX (639.17 ppb) > KVVIII (599.83 ppb). More correlation was seen for the solvent Vs extract yield whereas, the KVs revealed more correlation for the BM-fruit part (P = 0.05). The study comprehensively characterized the parts of fresh and dried BM-fruits in terms of extract yield and KVs amount.

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.

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.

Ultrasonic-assisted extraction of fenugreek flavonoids and its geographical-based comparative evaluation using green UHPLC-DAD analysis.

BACKGROUND: This study, for the first time, reports a simultaneous determination of flavonoids; rutin (RT), quercetin (QT), luteolin (LT), and kaempferol (KF) in different origins of fenugreek seeds samples (N = 45) using a green UHPLC-DAD analysis METHODOLOGY: Ultrasound-assisted extraction (UAE) was employed to extract fenugreek flavonoids using different polarity solvents of n-hexane (n-hex), dichloromethane (DCM), and methanol (MeOH) RESULTS: The extract yield on an individual basis was observed in the range of 1.03-17.29 mg, with the highest yield (mg/sample) for the Egyptian sample (17.29 mg). The highest total extract yield (mg/origin) was observed for the Iranian sample (82.28 ±â€¯5.38). The solvent with the highest extract yield (mg) was n-hex 169.35 ±â€¯13.47, followed by MeOH 114.39 ±â€¯12.27. The validated green UHPLC-DAD method resulted in a short runtime (9 min) with an accuracy of 97.86(±12.32)-101.37(±5.91), r2-values = 0.993-0.999, LOD = 2.09-4.48 ppm, and LOQ = 6.33-13.57 ppm for flavonoids analysis within the linearity range of 1-500 ppm. The general yield for flavonoids exhibited a descending order (ppm): RT (2924.55 ±â€¯143.84) > QT (457.05 ±â€¯34.07) > LT (82.37 ±â€¯3.27) > KF (4.54 ±â€¯0.00). The yield (ppm) for the flavonoids was more in MeOH solvent (3424.81 ±â€¯235.44) constructing a descending order of MeOH > n-hex > DCM. For an individual flavonoid yield; MeOH was seen with an order of RT > QT > LT, n-hex (LT > QT), and DCM (RT > LT > QT). The statistical analysis of PCA (principle component analysis) revealed a widespread distribution of flavonoids in fenugreek seeds with a variance of 35.93% (PC1). Moreover, flavonoids extraction was prone to the nature and specificity of the solvent used (PC2: 33.34%) rather than the amount of the extract yield (P = 0.00). The K-mean cluster analysis showed the origins with higher flavonoids yield in appropriate solvent as I3M (Indian accession # 3 MeOH extract) with more QT amount, IR2M (Iranian accession # 2 MeOH extract) with more LT amount along with I2M (Indian accession # 2 MeOH extract) and Q2M (Qassim Saudi Arabia accession # 2 MeOH extract) containing high amount of RT. The outcomes are supported by KMO (Kaiser-Meyer-Olkin) and Bartlett's test value of 0.56 with X2-value of 191.87 (P = 0.00) CONCLUSION: The samples were effectively evaluated and standardized in terms of flavonoid amount suggesting a significant variation in fenugreek quality.

Antidiabetic and Anticancer Potentials of Mangifera indica L. from Different Geographical Origins.

Mango fruit is well known for its nutritional and health benefits due to the presence of a plethora of phytochemical classes. The quality of mango fruit and its biological activities may change depending upon the variation in geographical factors. For the first time, this study comprehensively screened the biological activities of all four parts of the mango fruit from twelve different origins. Various cell lines (MCF7, HCT116, HepG2, MRC5) were used to screen the extracts for their cytotoxicity, glucose uptake, glutathione peroxidase activity, and α-amylase inhibition. MTT assays were carried out to calculate the IC50 values for the most effective extracts. The seed part from Kenya and Sri Lanka origins exhibited an IC50 value of 14.44 ± 3.61 (HCT116) and 17.19 ± 1.60 (MCF7). The seed part for Yemen Badami (119 ± 0.08) and epicarp part of Thailand (119 ± 0.11) mango fruit showed a significant increase in glucose utilization (50 µg/mL) as compared to the standard drug metformin (123 ± 0.07). The seed extracts of Yemen Taimoor seed (0.46 ± 0.05) and Yemen Badami (0.62 ± 0.13) produced a significant reduction in GPx activity (50 µg/mL) compared to the control cells (100 µg/mL). For α-amylase inhibition, the lowest IC50 value was observed for the endocarp part of Yemen Kalabathoor (108.8 ± 0.70 µg/mL). PCA, ANOVA, and Pearson's statistical models revealed a significant correlation for the fruit part vs. biological activities, and seed part vs. cytotoxicity and α-amylase activity (p = 0.05). The seed of mango fruit exhibited significant biological activities; hence, further in-depth metabolomic and in vivo studies are essential to effectively utilize the seed part for the treatment of various diseases.

The in vitro cytotoxicity against human melanoma cells, tyrosinase inhibition and antioxidant activity of Grewia tenax leaves extracts / La citotoxicidad in vitro contra las células de melanoma humano, inhibición de la tirosinasa y actividad antioxidante de los extractos de hojas de Grewia tenax

Grewia tenax (Forssk.) Fiori (Malvaceae) grows in the Arabian Peninsula and is used for several medicinal purposes. To characterize the dermatological bioactivities of G. tenax in terms of its antimelanoma, antityrosinase and antioxidant activities. Cytotoxicity was assessed by cell proliferation and mitochondrial viability assays. Ability to inhibit mushroom tyrosinase and scavenge free radicals were evaluated by an enzymatic and DPPH scavenging microtiter assay, respectively. Phytochemical analyses were carried out using TLC, HPLC-UV and NMR. The chloroform extract shown significant cytotoxic activity in terms of mitochondrial viability (43 ± 14 µg/mL). We identified lupeol and b-sitosterol as the main active components for the tyrosinase inhibitory activity of the hexane extract. Scavenging activity of the DPPH· radical was confined to the water extract. Extracts from this plant have the potential to be used as a base in the development of cosmeceutical products intended to whiten skin or to combat radical-induced physiopathological processes.

Grewia tenax (Forssk.) Fiori (Malvaceae) crece en la Península Arábiga y se utiliza con varios fines medicinales. Para caracterizar las bioactividades dermatológicas de G. tenax en cuanto a sus actividades antimelanoma, antitirosinasa y antioxidante; la citotoxicidad se evaluó mediante ensayos de proliferación celular y viabilidad mitocondrial. La capacidad para inhibir la tirosinasa de hongo y eliminar los radicales libres se evaluó mediante un ensayo de microtitulación enzimático y de eliminación de DPPH, respectivamente. Los análisis fitoquímicos se realizaron mediante TLC, HPLC-UV y NMR. El extracto de cloroformo mostró una actividad citotóxica significativa en términos de viabilidad mitocondrial (43 ± 14 µg/mL). Identificamos lupeol y b-sitosterol como los principales componentes activos para la actividad inhibitoria de tirosinasa del extracto de hexano. La actividad depuradora del radical DPPH· se limitó al extracto acuoso. Los extractos de esta planta tienen potencial para ser utilizados como base en el desarrollo de productos cosmecéuticos destinados a blanquear la piel o combatir procesos fisiopatológicos inducidos por radicales.

The effect of natural antioxidants, pH, and green solvents upon catechins stability during ultrasonic extraction from green tea leaves (Camellia sinensis).

BACKGROUND: This is a first-time report to evaluate the effect of natural antioxidants, pH, and green solvents upon catechins yield and stability during the active process of extraction from green tea leaves. METHODOLOGY: Green solvents (model-A) augmented with piperine (PPN) and quercetin (QT) as natural antioxidants (model-B) at different pH 2-6 (model-C) were used to extract catechins from green tea leaves using an ultrasonic extraction process (USE). For quantification of catechins (EC; epicatechins, ECG; epicatechin gallate, and EGCG; epigallocatechin gallate), a green and sensitive UHPLC-MS/MS method was developed and validated. RESULTS: The UHPLC-MS/MS method showed an accuracy of 98.3-102.6 % within the linearity range of 1-500 ppb for EC (m/z) 289 â†’ 245 â†’ 109, ECG (m/z) 441.2 â†’ 169 â†’ 289, and EGCG (m/z) 457.1 â†’ 169 â†’ 125.1. The general yield (ppb) for EC, ECG, and EGCG was observed with the ranges and sum of (N = 180) 0.06-157.80 and 6696.83, 0.04-316.93 and 12632.60 and, 0.12-584.11 and 26144.83, respectively. Model-C revealed the highest yield for catechins at the lowest pH-2 with an individual catechin yield of EGCG (584.11) > ECG (316.93) > EC (157.80) in CW2. In terms of stability, EGCG was the most unstable catechin whereas, catechins extracted in model-B exhibited more stability (%recovery of 14.70 for EC, 10.55 for ECG, and 5.36 for EGCG in BEP). Moreover, model-B showed the minimal degradation for catechins within the range of 11.81-94.64 (BEP); even the most degradable EGCG was seen with the smallest %loss of 11.81-94.64 at time 24-70 h, as compared to the loss of > 95 % in model-A and C. The ANOVA score for catechins yield was; F11,168 = 61.06 (EC), F11,168 = 66.53 (ECG), and F11,168 = 48.92 (EGCG) (P = 0.00) with mean scores of (M = 94.63, SD = 25.46) for EC, (M = 194.87, SD = 51.41) ECG, and (M = 357.57, SD = 96.80) EGCG in CE2. CONCLUSION: A significant effect on catechins yield and stability was observed with the use of natural antioxidants and lowest pH-2.

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.

Gas Chromatography-Mass Spectrometry (GC-MS) Metabolites Profiling and Biological Activities of Various Capsicum annum cultivars.

This study evaluates the quality variation for twenty-seven capsicum fruit (CF) samples, in terms of their volatile oil composition and biological activities. The GCMS analysis revealed the presence of seventy one chemical compounds from different chemical classes with an average (%) composition of: 26.13 (alcohols) > 18.82 (hydrocarbons) > 14.97 (esters) > 3.08 (ketones) > 1.14 (others) > 1.07 (acids) > 0.72 (sugar) > 0.42 (aldehydes) > 0.15 (amino compounds). Alcohols and hydrocarbons were the most abundant in these CF samples with 1-Decanol, 2-octyl- and docosanoic acid, docosyl ester as the major components, respectively. The % inhibition in cytotoxicity assays was observed in the range of 9−47 (MCF7) and 4−41 (HCT116) whereas, the zone of inhibition (mm) for the antimicrobial activity was found to be 0.0−17 (P. aeruginosa) > 0.0−13 (E. coli and S. aureus). Moreover, the samples with the largest zone of inhibition in the agar-well-diffusion method (C16, C19, and C26) upon further evaluation presented the least MIC and MBC values against P. aeruginosa with an MIC and MBC (µg/mL) of 6.3 and 12.5, respectively. The outcome for GCMS and biological activities were further supported by statistical tools of PCA and K-mean cluster analysis which confirmed the C16 CF sample with the best activity followed by C5, C13 (the best cytotoxic), and C19, C26 (the best antimicrobial). The statistical analysis exhibited a high Chi-square value of 5931.68 (GCMS) and 32.19 (biological activities) with p = 0.00 for KMO and Bartlett's Test of Sphericity. The 27-CF samples were effectively distinguished based on quality variation, and the C16 CF sample exhibited significant potential for further study.

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 ß-pinene, borneol, ɑ-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.

The vital role of animal, marine, and microbial natural products against COVID-19.

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.

Biological Screening of Glycyrrhiza glabra 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.

Ganoderma lucidum (Reishi) an edible mushroom; a comprehensive and critical review of its nutritional, cosmeceutical, mycochemical, pharmacological, clinical, and toxicological properties.

Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases 'Google scholar', 'Web of Science', 'ScienceDirect', 'PubMed', 'Springer Link', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/ß-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.

Green and novel ultrasonic extraction with UHPLC-MSMS analysis of natural sweetener (Glycyrrhizic acid) from Glycyrrhiza glabra; a multifactorial mechanistic evaluation based on statistical analysis.

A novel, green and eco-friendly, cost-effective, fast, and reliable high energy ultrasonication (US) extraction with UHPLC-MSMS (Ultrahigh performance liquid chromatography with mass spectrometry) quantification of Glycyrrhizic acid (GZA) is reported herein for the first time. The study provides useful insights regarding the effect of US-factors with statistical analysis and mechanisms, involved in GZA-extraction and analysis. An US-extraction method (US-MD) was developed using three levels of US factors: solvents (AC (acetone), EtOH (ethanol), H2O (water)), time (1, 2, 3 min), amplitudes (30, 40, 50%), pulse (10/0.5, 20/0.5, 30/0.5 sec), particle sizes (0.5, 1, 1.4 mm), and temperatures (20, 30, 40 °C). The US-MD was further validated with high accuracy 98.96 ± 6.82 and r2 = 0.995 whereas, an in-house analytical method (UHPLC-MSMS) was developed and validated to quantify the GZAamount. UHPLCMSMS-MD resulted in a retention time of 0.31 min with MSMS (821.400 > 351.200) in a 1 min run time whereas, UHPLCMSMS-MV showed high accuracy and precision with r2 = 0.998 for GZA. Statistical analysis of K-mean clustering finalized US-set-of-factors showing optimum extract yield (mg/1mg) of 0.48 with sum (2.41 ± 014) and mean (0.27) along with a high GZA-amount (µg/mg) of 8.23 with sum (43.31 ± 2.07) and mean (4.81) for H2O in 3 min at 40 °C using particle size (1.4 mm), amplitude (50%), and pulse (30/0.5). Large scale application of US-UHPLCMSMS confirmed the evaluation power of the method showing the order for GZA amount; Egypt > Pakistan > Syria > India > Palestine > America > Georgia > Morocco. A significant effect for US factors Vs extract yield and GZA amount was observed however, solvent*GZA-amount and extract yield*particle size were more significantly correlated compared to time*temperature*amplitude*pulse analyzed via PCA, GLM-UniANOVA, K-mean, and Pearson's correlation (P ≤ 0.05). A combined mechanism of shear stress, macroturbulence due to acoustic cavitation and implosions, sonochemical, and sonocapillary effect were noted for the US technique producing higher extract yield and GZA amount from licorice.

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 ß-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 α-pinene (31.3-62.5%) and δ-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.

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.

Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin.

Breast cancer is a complex and multi-drug resistant (MDR) disease, which could result in the failure of many chemotherapeutic clinical agents. Discovering effective molecules from natural products or by derivatization from known compounds is the interest of many research studies. The first objective of the present study is to investigate the cytotoxic combinatorial, chemosensitizing, and apoptotic effects of an isatin derived compound (5,5-diphenylimidazolidine-2,4-dione conjugated with 5-substituted isatin, named HAA2021 in the present study) against breast cancer cells (MCF7) and breast cancer cells resistant to doxorubicin (MCF7/ADR) when combined with doxorubicin. The second objective is to investigate the binding mode of HAA2021 withP-glycoprotein (P-gp) and heat shock protein 90 (Hsp90), and to determine whether their co-inhibition by HAA2021 contribute to the increase of the chemosensitization of MCF7/ADR cells to doxorubicin. The combination of HAA2021, at non-toxic doses, with doxorubicin synergistically inhibited the proliferation while inducing significant apoptosis in MCF7 cells. Moreover, HAA2021 increased the chemosensitization of MCF7/ADR cells to doxorubicin, resulting in increased cytotoxicity/selectivity and apoptosis-inducing efficiency compared with the effect of doxorubicin or HAA2021 alone against MCF7/ADR cells. Molecular modeling showed that two molecules of HAA2021 bind to P-gp at the same time, causing P-gp inhibitory effect of the MDR efflux pump, and accumulation of Rhodamine-123 (Rho123) in MCF7/ADR cells. Furthermore, HAA2021 stably interacted with Hsp90α more efficiently compared with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), which was confirmed with the surface plasmon resonance (SPR) and molecular modeling studies. Additionally, HAA2021 showed multi-target effects via the inhibition of Hsp90 and nuclear factor kappa B (NF-𝜅B) proteins in MCF7 and MCF7/ADR cells. Results of real time-PCR also confirmed the synergistic co-inhibition of P-gp/Hsp90α genes in MCF7/ADR cells. Further pharmacokinetic and in vivo studies are warranted for HAA2021 to confirm its anticancer capabilities.

Effects of Selected Nigerian Medicinal Plants on the Viability, Mobility, and Multidrug-Resistant Mechanisms in Liver, Colon, and Skin Cancer Cell Lines.

Medicinal plants indicated for chronic diseases usually have good safety margins as they are intended for lifelong treatments. We hypothesized that they may provide patients with baseline protection to cancers and multidrug resistance-reversing phytochemicals resulting in successful prevention and/or adjuvant treatment of chemotherapy-resistant cancers. We selected 27 popular herbal infusions widely used in Nigeria for diabetes and studied their effects on a panel of liver (HepG2), colon (Caco2), and skin (B16-F10) cancer cells. Cytotoxicity was measured using the SRB staining assay. The 2D antimigratory effect was evaluated using an Oris™ platform. The P-glycoprotein (P-gp) efflux activity was evaluated using Rh-123 as a fluorescent probe. The inhibition of tyrosinase-mediated melanogenesis was evaluated by colorimetric enzymatic assays. Our results show that melanoma cell proliferation was strongly inhibited by Anogeissus leiocarpus (Combretaceae), Bridelia ferruginea (Phyllanthaceae), D. ogea (Leguminosae), and Syzygium guineense (Myrtaceae) extracts (GI50 = 50 µg/ml). Alstonia boonei (Apocynaceae), Gongronema latifolium (Asclepiadaceae), and Strophanthus hispidus (Apocynaceae) were preferentially toxic against Caco2 (GI50 = 50, 5 and 35 µg/ml, respectively). The most active extracts against different drug resistance mechanisms were B. ferruginea (inhibition of P-gp efflux, and impairing tyrosinase activity) and X. americana (inhibition of P-gp efflux). A. leiocarpus, Kaya senegalensis (Meliaceae), S. guineense, and Terminalia avicennioides (Combretaceae) significantly inhibited B16-F10 cell migration. Lupeol, ursolic acid, quercitrin, epicatechin, gallic acid, and ellagic acid were dereplicated by HPLC and HPTLC as their bioactive phytochemicals. In conclusion, the above in-vitro activities of herbal infusions regularly consumed by Nigerian diabetic patients may either act as a baseline chemoprotection or as sensitizing agents.