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.

A Review of the Anti-Obesity Effects of Wild Edible Plants in the Mediterranean Diet and Their Active Compounds: From Traditional Uses to Action Mechanisms and Therapeutic Targets.

Obesity is a long-term condition resulting from a continuous imbalance between the amount of energy consumed and expended. It is associated with premature mortality and contributes to a large portion of the global chronic disease burden, including diabesity, cardiovascular disease, hypertension, and some cancers. While lifestyle changes and dietary adjustments are the primary ways to manage obesity, they may not always be sufficient for long-term weight loss. In these cases, medication may be necessary. However, the options for drugs are limited due to their potential side effects. As a result, there is a need to identify safe and effective alternative treatments. Recently, dietary compounds, plants, and bioactive phytochemicals have been considered as promising sources for discovering new pharmacological agents to treat obesity and its related complications. These natural products can function independently or synergistically with other plants to augment their effects at various levels of the body. They can modulate appetite, lipase activity, thermogenesis and fat synthesis and degradation, satiation, adipogenesis, and adipocyte apoptosis. Additionally, targeting adipocyte growth and differentiation with diverse medicinal plants/diet is a significant strategy for devising new anti-obesity drugs that can intervene in preadipocytes, maturing preadipocytes, and mature adipocytes. Clinical trials have shown that the wild edible plants in the Mediterranean diet can reduce the risk of obesity and its related diseases. This review examines the effectiveness of the common components of the Mediterranean diet in managing obesity and its associated health issues. We conducted a comprehensive literature review using PubMed, Science Direct, Google Scholar, and Medline Plus to gather data on the therapeutic effects of the Mediterranean diet and phytochemicals in treating obesity and its associated diseases.

In Vitro Evaluation of Chemically Analyzed Hypericum Triquetrifolium Extract Efficacy in Apoptosis Induction and Cell Cycle Arrest of the HCT-116 Colon Cancer Cell Line.

Naturally derived drugs and plant-based products are attractive commodities that are being explored for cancer treatment. This in vitro study aimed to investigate the role of Hypericum triquetrifolium (50% ethanol: 50% water) extract (HTE) treatment on apoptosis, cell cycle modulation, and cell cycle arrest in human colon cancer cell line (HCT-116). HTE induced cell death via an apoptotic process, as assayed by an Annexin V-Cy3 assay. Exposing HCT-116 cells to 0.064, 0.125, 0.25, and 0.5 mg/mL of HTE for 24 h led to 50 ± 9%, 71.6 ± 8%, 85 ± 5%, and 96 ± 1.5% apoptotic cells, respectively. HCT-116 cells treated with 0.25 and 0.5 mg/mL HTE for 3 h resulted in 38.9 ± 1.5% and 57.2 ± 3% cleavage of caspase-3-specific substrate, respectively. RT-PCR analysis revealed that the HTE extract had no effect on mRNA levels of Apaf-1 and NOXA. Moreover, the addition of 0.125 mg/mL and 0.25 mg/mL HTE for 24 h was clearly shown to attenuate the cell cycle progression machinery in HCT-116 cells. GC/MS analysis of the extract identified 21 phytochemicals that are known as apoptosis inducers and cell cycle arrest agents. All the compounds detected are novel in H. triquetrifolium. These results suggest that HTE-induced apoptosis of human colon cells is mediated primarily through the caspase-dependent pathway. Thus, HTE appears to be a potent therapeutic agent for colon cancer treatment.

Refugees in Conflict: Creating a Bridge Between Traditional and Conventional Health Belief Models.

The recent wave of migration from Middle Eastern countries to Europe presents significant challenges to the European health profession. These include the inevitable communication gap created by differences in health care beliefs between European oncologists, health care practitioners, and refugee patients. This article presents the conclusions of a workshop attended by a group of clinicians and researchers affiliated with the Middle East Cancer Consortium, as well as four European-based health-related organizations. Workshop participants included leading clinicians and medical educators from the field of integrative medicine and supportive cancer care from Italy, Germany, Turkey, Israel, Palestine, Iran, Lebanon, Jordan, Egypt, and Sudan. The workshop illustrated the need for creating a dialogue between European health care professionals and the refugee population in order to overcome the communication barriers to create healing process. The affinity for complementary and traditional medicine (CTM) among many refugee populations was also addressed, directing participants to the mediating role that integrative medicine serves between CTM and conventional medicine health belief models. This is especially relevant to the use of herbal medicine among oncology patients, for whom an open and nonjudgmental (yet evidence-based) dialogue is of utmost importance. The workshop concluded with a recommendation for the creation of a comprehensive health care model, to include bio-psycho-social and cultural-spiritual elements, addressing both acute and chronic medical conditions. These models need to be codesigned by European and Middle Eastern clinicians and researchers, internalizing a culturally sensitive approach and ethical commitment to the refugee population, as well as indigenous groups originating from Middle Eastern and north African countries. IMPLICATIONS FOR PRACTICE: European oncologists face a communication gap with refugee patients who have recently immigrated from Middle Eastern and northern African countries, with their different health belief models and affinity for traditional and herbal medicine. A culturally sensitive approach to care will foster doctor-refugee communication, through the integration of evidence-based medicine within a nonjudgmental, bio-psycho-social-cultural-spiritual agenda, addressing patients' expectation within a supportive and palliative care context. Integrative physicians, who are conventional doctors trained in traditional/complementary medicine, can mediate between conventional and traditional/herbal paradigms of care, facilitating doctor-patient communication through education and by providing clinical consultations within conventional oncology centers.

Potential risks associated with traditional herbal medicine use in cancer care: A study of Middle Eastern oncology health care professionals.

BACKGROUND: The authors assessed the use of herbal medicine by Middle Eastern patients with cancer, as reported by their oncology health care professionals (HCPs). Herbal products identified by the study HCPs were evaluated for potential negative effects. METHODS: Oncology HCPs from 16 Middle Eastern countries received a 17-item questionnaire asking them to list 5 herbal products in use by their patients with cancer. A literature search (PubMed, Micromedex, AltMedDex, and the Natural Medicine Comprehensive Database) was conducted to identify safety-related concerns associated with the products listed. RESULTS: A total of 339 HCPs completed the study questionnaire (response rate of 80.3%), identifying 44 herbal and 3 nonherbal nutritional supplements. Safety-related concerns were associated with 29 products, including herb-drug interactions with altered pharmacodynamics (15 herbs), direct toxic effects (18 herbs), and increased in vitro response of cancer cells to chemotherapy (7 herbs). CONCLUSIONS: Herbal medicine use, which is prevalent in Middle Eastern countries, has several potentially negative effects that include direct toxic effects, negative interactions with anticancer drugs, and increased chemosensitivity of cancer cells, requiring a reduction in dose-density. Oncology HCPs working in countries in which herbal medicine use is prevalent need to better understand the implications of this practice. The presence of integrative physicians with training in complementary and traditional medicine can help patients and their HCPs reach an informed decision regarding the safety and effective use of these products.

Integration of complementary medicine in supportive cancer care: survey of health-care providers' perspectives from 16 countries in the Middle East.

INTRODUCTION: In this multinational Middle-Eastern study, we assessed health-care providers' (HCPs) perspectives on their patients' use of complementary and traditional medicine (CTM) and identified the leading barriers to CTM integration in supportive cancer care. METHODS: A 17-item questionnaire was developed and administered to HCPs attending palliative medicine workshops conducted across the Middle East by the Middle East Cancer Consortium. RESULTS: 339 HCPs from 16 countries across the Middle East completed the questionnaire (80.3 % response rate). Respondents perceived their patients' reasons for CTM use primarily in the context of cancer cure (63 %) and quality of life (QOL) improvement (57 %). Expectation regarding CTM's role in cancer cure/survival was more pronounced in Turkey, Jordan, the Palestinian Authority, and the Persian Gulf area. In contrast, the expectation that CTM would improve QOL was more emphasized in Israel. A mid-position between the cure/survival and QOL poles was observed in Cyprus, Lebanon, and the North African countries. Leading barriers to CTM integration in supportive cancer care included oncologists' skepticism and a gap between patients' expectations and HCP's objectives. Respondents' leading recommendation to HCPs was to communicate integrative care emphasizing well-being and improved functioning in accordance with their patients' health beliefs. CONCLUSION: CTM integration in supportive cancer care can be facilitated by implementing a platform for Middle Eastern clinical collaborations. HCPs' expectations and experiences with CTM have been positive in the oncology setting. These data need to be corroborated with information of patients' expectations on the provision of CTM over all phases of the oncology treatment.

[Modeling integrative oncology care program for Arab patients in north Israel: towards quality of life improvement during chemotherapy].

BACKGROUND: In the last decade, a number of integrative oncology programs have been established within leading oncology departments in Israel aiming to provide consultations that address patients' concerns and improve their quality of life (QOL). OBJECTIVE: To identify Arab cancer patients' attitudes, needs and expectations concerning integration of complementary and traditional medicine (CTM) in their supportive oncology care. METHODS: This article presents studies based on both qualitative (including interviews with patients, oncologists and CTM practitioners) and quantitative studies which were designed to evaluate patients' attitudes, needs and expectations regarding CTM integration in supportive oncology care. RESULTS: Of the 313 Arab respondents, 109 reported on the use of herbal medicine for cancer-associated outcomes. Over 78% of respondents considered QOL improvement as their main expectation of integrated CM consultation. Similar expectations were expressed in studies exploring 155 cancer care practitioners in Israel and Arab countries, 27 CTM-trained Arab practitioners, and a sample of 15 Arab patients referred to integrative medicine consultation. CONCLUSIONS: Arab cancer patients support QOL-oriented integrated medicine programs provided in oncology settings. Integrative medicine consultation should provide patients with an evidence-based recommendation on efficacy and safety of herbs commonly used concomitant with chemotherapy. We recommend designing integrative oncology training courses for physicians who will provide evidence-based consultation attuned with Arab patients' needs, concerns and cultural-sensitive orientation.

Occult Pancreatic Neuroendocrine Tumor Presenting as Carcinoid Syndrome.

We present a case of a 50-year-old male who initially presented to the clinic with complaints of palpitations, shortness of breath, dizziness, night sweats, headaches with associated intermittent episodes of diarrhea, episodes of flushing, and rash on the upper body. Laboratory testing revealed elevated chromogranin A levels. Initial imaging with computed tomography (CT) of the abdomen and pelvis with contrast was negative for any lesions. However, due to his clinical presentation and high suspicion of a neuroendocrine tumor (NET), a positron emission tomography-CT (PET-CT) scan with Gallium 68-DOTATATE was obtained, confirming and localizing his NET in the neck of the pancreas and the liver. Following confirmation and localization of his tumor, he was referred for surgical evaluation and treatment. Pancreatic neuroendocrine tumors are rare and difficult to diagnose, highlighted by unsuccessful initial efforts to localize and confirm the tumor. This case underscores the importance of clinical suspicion and acumen in diagnosing neuroendocrine tumors. Upcoming imaging modalities of PET-CT scans provide promising avenues to uncover neuroendocrine tumors.

Management of Obesity-Related Inflammatory and Cardiovascular Diseases by Medicinal Plants: From Traditional Uses to Therapeutic Targets.

Inflammation is a crucial factor in the development and progression of cardiovascular diseases (CVD). Cardiac remodeling in the presence of persistent inflammation leads to myocardial fibrosis and extracellular matrix changes, which reduce cardiac function, induce arrhythmias, and finally, cause heart failure. The majority of current CVD treatment plans concentrate on reducing risk factors such as hyperlipidemia, type 2 diabetes, and hypertension. One such strategy could be inflammation reduction. Numerous in vitro, animal, and clinical studies indicate that obesity is associated with low-grade inflammation. Recent studies have demonstrated the potential of medicinal plants and phytochemicals to cure and prevent obesity and inflammation. In comparison to conventional therapies, the synergistic effects of several phytochemicals boost their bioavailability and impact numerous cellular and molecular targets. Focusing on appetite, pancreatic lipase activity, thermogenesis, lipid metabolism, lipolysis and adipogenesis, apoptosis in adipocytes, and adipocyte life cycle by medicinal plants and phytochemicals represent an important goal in the development of new anti-obesity drugs. We conducted an extensive review of the literature and electronic databases, including Google Scholar, PubMed, Science Direct, and MedlinePlus, for collecting data on the therapeutic effects of medicinal plants/phytochemicals in curing obesity and its related inflammation and CVD diseases, including cellular and molecular mechanisms, cytokines, signal transduction cascades, and clinical trials.

Traumatic occult pneumothorax and ipsilateral hydatid cyst: A case report.

INTRODUCTION: Traumatic pneumothorax is a common chest condition that can be caused by a chest trauma. Hydatid cysts are also common, especially in Syria, and is caused by Echinococcus granulosis infection. CASE PRESENTATION: We report a case of mutual presentation of pneumothorax and a large Hydatid cyst on the same chest side in an 18 years-old patient who got stabbed in the chest. The chest x-ray reveled well-defined, homogeneous radio-opacity lesion that is consistent with Hydatid cyst but no pneumothorax was observed. Later, the chest CT showed a small pneumothorax that coexist with the Hydatid cyst. The case was treated conservatively and the patient survived. DISCUSSION: Some studies support treating asymptomatic trauma patients with occult PT with observation and placing a chest tube if still asymptomatic. Our case questions the management protocol for such a rare encounter as the stability status of the patient was poor, and there was a large hydatid cyst close to the chest wall. CONCLUSION: Physicians should be aware of the possible management solutions when dealing with similar cases, especially in emergency settings. Until clear guidelines are published for this matter, we recommend that high-level observation of the patient's vitals are the determining factor for suitable intervention.

Greco-arab and islamic herbal-derived anticancer modalities: from tradition to molecular mechanisms.

The incidence of cancer is increasing in the developed countries and even more so in developing countries parallel to the increase in life expectancy. In recent years, clinicians and researchers advocate the need to include supportive and palliative care since the establishment of the diagnosis and throughout the duration of treatment, with the goal of improving patients' quality of life. This patient-centered approach in supportive care is also shared by various traditional and complementary medicine approaches. Traditional Arab-Islamic medicine offers a variety of therapeutic modalities that include herbal, nutritional, and spiritual approaches. Physicians and scholars, such as Avicenna (980-1037), Rhazes (965-915), Al Zahrawi (936-1013), and Ibn al Nafis (1218-1288) referred to cancer etiology in various medicinal texts and suggested both preventive and therapeutic remedies to alleviate suffering. This review presents research data related to the anticancer activities of herbs used in Arab-Islamic medicine and allude to their potential role in improving the quality of life of cancer patients.

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.

Weight loss in animals and humans treated with "weighlevel", a combination of four medicinal plants used in traditional arabic and islamic medicine.

Weighlevel, a mixture of extract of four plants used in traditional Arabic and Islamic medicine as well as in European herbal medicine, was prepared and assessed for its safety and efficacy in weight loss. Leaves of Alchemilla vulgaris, Olea europaea and Mentha longifolia L., as well as seeds of Cuminum cyminum, were used. Cultured human fibroblasts treated with Weighlevel did not exhibit any sign of toxicity as evidenced by lactate dehydrogenase release. These results were confirmed in experimental studies on rats where an LD(50) of 15.3 g kg(-1) was observed. Significant antioxidant properties were seen at very low concentrations of Weighlevel (10 µg ml(-1)) as measured by the lipid peroxidation method. Progressive and significant weight loss was observed in chickens given this mixture weekly for 4 weeks compared with controls. Furthermore, a 3-fold increase in the thermogenesis was seen in rat interscapular brown adipose tissue following exposure to different concentrations of Weighlevel extract as determined by measurement of increased oxygen consumption. In addition, a clinical study was carried out among 80 human volunteers with a body mass index (BMI) of 30.67 ± 2.14 kg m(-2). All 80 subjects were asked to continue their usual diet but to eat only three main meals daily and to take one Weighlevel tablet 30 min before each meal. Fourteen subjects were excluded for not following the protocol, and 66 subjects were all evaluated for efficacy and tolerability of Weighlevel monthly for 3 months. Weighlevel was well tolerated by all subjects, and no side effects were reported. A progressive and significant weight loss was seen in these subjects during the whole study period. Higher levels of weight loss were seen in people with BMI of 25-30 kg m(-2) (overweight) compared to people with BMI >30 kg m(-2) (obese). The BMI was reduced after 3 months from 28.5 ± 1.2 and 32.1 ± 1.8 kg m(-2) to 24.5 ± 1.4 and 27.5 ± 2.2 kg m(-2) in overweight and obese group, respectively. Results indicate safety, tolerability and efficacy of Weighlevel.

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.

Traditional Arabic and Islamic Medicine, a Re-emerging Health Aid.

Complementary medicine is a formal method of health care in most countries of the ancient world. It is expected to become more widely integrated into the modern medical system, including the medical curriculum. Despite the perception of modern medicine as more efficacious, traditional medicine continues to be practiced. More than 70% of the developing world's population still depends primarily on the complementary and alternative systems of medicine (CAM). In rural areas, cultural beliefs and practices often lead to self-care, home remedies or consultation with traditional healers. Herbal medicine can be broadly classified into four basic systems as follows: Traditional Chinese Herbalism, Ayurvedic Herbalism, Western Herbalism-which originally came from Greece and Rome to Europe and then spread to North and South America and Traditional Arabic and Islamic Medicine (TAIM). There is no doubt that today the concept of Arabic traditional herbal medicine is a part of modern life in the Middle East, and it is acquiring worldwide respect, with growing interest among traditional herbalists and the scientific community. TAIM therapies have shown remarkable success in healing acute as well as chronic diseases and have been utilized by people in most countries of the Mediterranean who have faith in spiritual healers. TAIM is the first choice for many in dealing with ailments such as infertility, epilepsy, psychosomatic troubles and depression. In parallel, issues of efficacy and safety of complementary medicine have become increasingly important and supervision of the techniques and procedures used is required for commercial as well as traditional uses. More research is therefore needed to understand this type of medicine and ensure its safe usage. The present review will discuss the status of traditional Arab medicine (particularly herbal medicine), including the efficacy and toxicity of specific medicinal preparations, with an emphasis on the modern in vitro and in vivo techniques.

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.

Metabolic and Epigenetic Action Mechanisms of Antidiabetic Medicinal Plants.

Diabetes is a predominant metabolic disease nowadays due to the off-beam lifestyle of diet and reduced physical activity. Complications of the illness include the gene-environment interactions and the downstream genetic and epigenetic consequences, e.g., cardiovascular diseases, tumor progression, retinopathy, nephropathy, neuropathy, polydipsia, polyphagia, polyuria, and weight loss. This review sheds the light on the mechanistic insights of antidiabetic medicinal plants in targeting key organs and tissues involved in regulating blood glucose homeostasis including the pancreas, liver, muscles, adipose tissues, and glucose absorption in the intestine. Diabetes is also involved in modulating major epigenetic pathways such as DNA methylation and histone modification. In this respect, we will discuss the phytochemicals as current and future epigenetic drugs in the treatment of diabetes. In addition, several proteins are common targets for the treatment of diabetes. Some phytochemicals are expected to directly interact with these targets. We lastly uncover modeling studies that predict such plausible interactions. In conclusion, this review article presents the mechanistic insight of phytochemicals in the treatment of diabetes by combining both the cellular systems biology and molecular modeling.

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.