How Thymoquinone from Nigella sativa Accelerates Wound Healing through Multiple Mechanisms and Targets.

Wound healing is a multifaceted process necessitating the collaboration of numerous elements to mend damaged tissue. Plant and animal-derived natural compounds have been utilized for wound treatment over the centuries, with many scientific investigations examining these compounds. Those with antioxidant, anti-inflammatory, and antibacterial properties are particularly noteworthy, as they target various wound-healing stages to expedite recovery. Thymoquinone, derived from Nigella sativa (N. sativa)-a medicinal herb with a long history of use in traditional medicine systems such as Unani, Ayurveda, Chinese, and Greco-Arabic and Islamic medicine-has demonstrated a range of therapeutic properties. Thymoquinone exhibits antimicrobial, anti-inflammatory, and antineoplastic activities, positioning it as a potential remedy for skin pathologies. This review examines recent research on how thymoquinone accelerates wound healing and the mechanisms behind its effectiveness. We carried out a comprehensive review of literature and electronic databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus. Our aim was to gather relevant papers published between 2015 and August 2023. The main criteria for inclusion were that the articles had to be peer reviewed, original, written in English, and discuss the wound-healing parameters of thymoquinone in wound repair. Our review focused on the effects of thymoquinone on the cellular and molecular mechanisms involved in wound healing. We also examined the role of cytokines, signal transduction cascades, and clinical trials. We found sufficient evidence to support the effectiveness of thymoquinone in promoting wound healing. However, there is no consensus on the most effective concentrations of these substances. It is therefore essential to determine the optimal treatment doses and the best route of administration. Further research is also needed to investigate potential side effects and the performance of thymoquinone in clinical trials.

Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds.

This study explores the effects of the Mediterranean diet, herbal remedies, and their phytochemicals on various gastrointestinal conditions and reviews the global use of medicinal plants for common digestive problems. The review highlights key plants and their mechanisms of action and summarizes the latest findings on how plant-based products influence the digestive system and how they work. We searched various sources of literature and databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus. Our focus was on gathering relevant papers published between 2013 and August 2023. Certain plants exhibit potential in preventing or treating digestive diseases and cancers. Notable examples include Curcuma longa, Zingiber officinale, Aloe vera, Calendula officinalis, Lavandula angustifolia, Thymus vulgaris, Rosmarinus officinalis, Ginkgo biloba, Cynodon dactylon, and Vaccinium myrtillus. The phytochemical analysis of the plants showed that compounds such as quercetin, anthocyanins, curcumin, phenolics, isoflavones glycosides, flavonoids, and saponins constitute the main active substances within these plants. These natural remedies have the potential to enhance the digestive system and alleviate pain and discomfort in patients. However, further research is imperative to comprehensively evaluate the benefits and safety of herbal medicines to use their active ingredients for the development of natural and effective drugs.

Anti-Diabesity Middle Eastern Medicinal Plants and Their Action Mechanisms.

Over the last four decades, the escalation in diabetes and obesity rates has become epidemic all over the world. Diabesity describes the strong link between T2D and obesity. It correlates deeper with the elevated risks of developing cardiovascular disease hypertension, stroke, and several malignancies. Therapeutic usage of medicinal plants and natural products in the treatment of diabetes and obesity has long been known to physicians of Greco-Arab and Islamic medicine. Improved versions of their abundant medicinal plant-based formulations are at present some of the most popular herbal treatments used. Preclinical and clinical data about medicinal plants along with their bioactive constituents are now available, justifying the traditionally known therapeutic uses of products derived from them for the prevention and cure of obesity-related T2D and other health problems. The aim of this review is to systematize published scientific data dealing with the efficiency of active ingredients or extracts from Middle Eastern medicinal plants and diet in the management of diabesity and its complications. Google Scholar, MEDLINE, and PubMed were searched for publications describing the medicinal plants and diet used in the management of T2D, obesity, and their complications. The used keywords were "medicinal plants" or "herbals" in combination with "obesity," "diabetes," "diabetes," or nephropathy. More than 130 medicinal plants were identified to target diabesity and its complications. The antidiabetic and anti-obesity effects and action mechanisms of these plants are discussed here. These include the regulation of appetite, thermogenesis, lipid absorption, and lipolysis; pancreatic lipase activity and adipogenesis; glucose absorption in the intestine, insulin secretion, glucose transporters, gluconeogenesis, and epigenetic mechanisms.

Hypericum triquetrifolium-Derived Factors Downregulate the Production Levels of LPS-Induced Nitric Oxide and Tumor Necrosis Factor-α in THP-1 Cells.

Based on knowledge from traditional Arab herbal medicine, this in vitro study aims to examine the anti-inflammatory mechanism of Hypericum triquetrifolium by measuring the expression and release of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6), and inducible nitric oxide synthase (iNOS) in human monocytic cells, THP-1. The effects were assessed by measuring the levels of secretory proteins and mRNA of TNF-α and IL-6, the levels of nitric oxide (NO) secretion and the expression of iNOS in THP-1 cells. Cells were treated with 5 µg lipopolysaccharide/ml (LPS) in the presence and absence of increasing concentrations of extracts from the aerial parts of H. triquetrifolium. During the entire experimental period, we used extract concentrations (up to 250 µg mL(-1)) that had no cytotoxic effects, as measured with MTT and LDH assays. Hypericum triquetrifolium extracts remarkably suppressed the LPS-induced NO release, significantly attenuated the LPS-induced transcription of iNOS and inhibited in a dose-dependent manner the expression and release of TNF-α. No significant effects were observed on the release of IL-6. Taken together, these results suggest that H. triquetrifolium probably exerts anti-inflammatory effects through the suppression of TNF-α and iNOS expressions.

Metabolic and Epigenetics Action Mechanisms of Antiobesity Medicinal Plants and Phytochemicals.

Ever-growing research efforts are demonstrating the potential of medicinal plants and their phytochemicals to prevent and manage obesity, either individually or synergistically. Multiple combinations of phytochemicals can result in a synergistic activity that increases their beneficial effects at molecular, cellular, metabolic, and temporal levels, offering advantages over chemically synthesized drug-based treatments. Herbs and their derived compounds have the potential for controlling appetite, inhibiting pancreatic lipase activity, stimulating thermogenesis and lipid metabolism, increasing satiety, promoting lipolysis, regulating adipogenesis, and inducing apoptosis in adipocytes. Furthermore, targeting adipocyte life cycle using various dietary bioactives that affect different stages of adipocyte life cycle represents also an important target in the development of new antiobesity drugs. In this regard, different stages of adipocyte development that are targeted by antiobesity drugs can include preadipocytes, maturing preadipocytes, and mature adipocytes. Various herbal-derived active compounds, such as capsaicin, genistein, apigenin, luteolin, kaempferol, myricetin, quercetin, docosahexaenoic acid, quercetin, resveratrol, and ajoene, affect adipocytes during specific stages of development, resulting in either inhibition of adipogenesis or induction of apoptosis. Although numerous molecular targets that can be used for both treatment and prevention of obesity have been identified, targeted single cellular receptor or pathway has resulted in limited success. In this review, we discuss the state-of-the-art knowledge about antiobesity medicinal plants and their active compounds and their effects on several cellular, molecular, and metabolic pathways simultaneously with multiple phytochemicals through synergistic functioning which might be an appropriate approach to better management of obesity. In addition, epigenetic mechanisms (acetylation, methylation, miRNAs, ubiquitylation, phosphorylation, and chromatin packaging) of phytochemicals and their preventive and therapeutic perspective are explored in this review.

In Vitro and Randomized, Double-Blind, Placebo-Controlled Trial to Determine the Efficacy and Safety of Nine Antiacne Medicinal Plants.

The present in vitro and randomized, double-blind, placebo-controlled trial aims to determine the efficacy and safety of nine Mediterranean antiacne medicinal plants. The antimicrobial, antisebum, and anti-inflammatory activities of the plant extracts were evaluated in cells from the immortalized human keratinocytes (HaCaT) and human monocytic cell line (THP-1) as well as in a double-blind, randomized, and placebo-controlled trial. Most of the extracts showed no significant cytotoxic effects on HaCaT cells up to 250 µg/ml. Inula helenium (IH) and Saponaria officinalis (SO) inhibited sebum production at 90 µg/ml and 30 µg/ml, respectively. The inhibition effect of SO on the growth of Cutibacterium acnes was 1.2 times higher than that of chloramphenicol. IH and SO extracts significantly inhibited the lipopolysaccharide- (LPS-) induced IL-6 and TNF-α production in THP-1 cells reaching the control levels of untreated cells at a concentration of 250 µg/ml. SO, IH, and Solanum nigrum (SN) extracts inhibited the nitric oxide (NO) production in a dose-dependent manner. Based on these results, an antiacne herbal cream (AHC) was prepared from different portions of extracts from SO, IH, and SN, and its efficacy was evaluated in a double-blind, randomized, and controlled efficacy study with 41 acne patients, ages 18-24, who were asked to apply AHC (n = 27) or a placebo (n = 14) two to three times daily for six weeks. Results obtained indicate that the AHC has unique synergistic effects that halt sebum production, combined with highly antiseptic and anti-inflammatory activity, in which 54.95% (t = 19.37 P < 0.001) of acne inflammatory and noninflammatory lesions disappeared after two weeks, 85.3%, after five weeks (t = 14.19 P < 0.001), and 91.4%, at the end of the sixth week of application (t = 5.7 P < 0.001). In conclusion, SO, IH, and SN as single extracts and in combination as AHC showed significant antimicrobial, antisebum, and anti-inflammatory activities in vitro and in a double-blind, randomized, and controlled antiacne efficacy. Therefore, AHC represents an interesting alternative treatment for acne.

Chemical Analysis and Cytotoxic and Cytostatic Effects of Twelve Honey Samples Collected from Different Regions in Morocco and Palestine.

The aim of this in vitro study is to characterize the phenolic compounds of twelve honey samples collected from different locations in Palestine (H1-6) and Morocco (H7-12) and to evaluate their cytotoxic and cytostatic effects in cells from the human colorectal carcinoma cell line HCT-116 and breast cancer cell line MCF-7. Quantitative HPLC analysis revealed nine phenolic compounds in three Moroccan honey samples, namely, syringic acid, tannic acid, caffeic acid, ferulic acid, coumaric acid, gallic acid, rosmarinic acid, epicatechin, and pyrogallol. Syringic acid, abundant in numerous types of honey with strong antioxidant capacities, was present at values ranging between 0.10 mg/100 g and 1.24 mg/100 g of Daghmos (H11) and Kabbar (H10) samples, respectively. No significant reductions in cell viability were observed in both cell lines treated with the Palestinian samples as measured with MTT assay. Significant cytostatic effects were after treatment of HCT cells with Morar honey H1 with IC50 of 1789 µg/ml. Three Moroccan samples, H7 (Zaâtar), H9 (Bochnikha), and H10 (Kabbar), showed slight, but significant cytostatic effects in HCT cells. A strong correlation was observed between cytostatic activity of MCF cells and antioxidant content (phenols, flavonoids, and flavonol). Furthermore, a strong negative correlation was detected between the cytostatic activity in HCT cells and the contents of syringic acid (r= -0.756) and tannic acid (r= -0.610). These results indicate that the traditionally known anticancer effects of honey might be mediated in part through cytostatic effects.

In Vitro Evaluation of the Potential Use of Propolis as a Multitarget Therapeutic Product: Physicochemical Properties, Chemical Composition, and Immunomodulatory, Antibacterial, and Anticancer Properties.

Propolis is a resin that honeybees produce by mixing saliva and beeswax with exudate gathered from botanical sources. The present in vitro study investigated the potential use of propolis as a multitarget therapeutic product and the physicochemical properties, chemical composition, and immunomodulatory, antioxidant, antibacterial, and anticancer properties of a propolis extract from the northern Morocco region (PNM). Pinocembrin, chrysin, and quercetin were the main phenolic compounds of PNM as measured in HPLC. The PNM showed significant inhibitory effects against all tested Gram-positive and Gram-negative strains and showed high antioxidant activities by scavenging free radicals with IC50 (DPPH = 0.02, ABTS = 0.04, and FRAP = 0.04 mg/ml). In addition, PNM induced a dose-dependent cytostatic effect in MCF-7, HCT, and THP-1 cell lines at noncytotoxic concentrations with IC50 values of 479.22, 108.88, and 50.54 µg/ml, respectively. The production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) was decreased in a dose-dependent manner in LPS-stimulated human peripheral blood mononuclear cells (PBMNCs), whereas the production of the anti-inflammatory interleukin-10 (IL-10) was increased in a dose-dependent manner reaching 15-fold compared to the levels measured in untreated PBMNCs. Overall, the results showed that the traditionally known multitarget therapeutic properties of the PNM seem to be mediated, at least in part, through cytostatic, antibacterial, and immunomodulatory effects.