Molecular Mechanisms of Anti-Inflammatory Phytochemicals 2.0.

Inflammation is currently the most investigated cell response, not only for the frequency with which it occurs but essentially due to the growing incidence of inflammatory diseases, increasingly labeled as characteristics of modern society [...].

Medicinal Plant-Derived Phytochemicals in Detoxification.

The average worldwide human life expectancy is 70 years, with a significantly higher value in Western societies. Many modern diseases are not associated with premature mortality but with a decreased quality of life in aged patients and an excessive accumulation of various toxic compounds in the human body during life. Today, scientists are especially interested in finding compounds that can help increase a healthy lifespan by detoxifying the body. Phytotherapy with specific approaches is used in alternative medicine to remove toxins from the body. Worldwide, research is conducted to identify medicinal plant-derived molecules that, with few or no side effects, may protect the liver and other organs. This review provides updated information about the detoxification process, the traditional and modern use of the most effective medicinal plants, their active metabolites as detoxifying agents, and the mechanisms and pathways involved in the detoxification process. Among medicinal plants with substantial detoxifying properties, a major part belongs to the Asteraceae family (Silybum marianum, Cynara scolymus, Arctium lappa, Helichrysum spp, Inula helenium, and Taraxacum officinale). The most widely used hepatoprotective phytocomponent is silymarin, a standardized extract from the Silybum marianum seeds containing a mixture of flavonolignans. Many polysaccharides, polyphenols, and terpenoids have a detoxifying effect. Overall, scientific data on medicinal plants used in phytotherapeutic practice worldwide provides an understanding and awareness of their efficacy in detoxification.

Riparin-B as a Potential Inhibitor of AdeABC Efflux System from Acinetobacter baumannii.

Acinetobacter baumannii is an important opportunistic pathogen that causes serious health-related infections, especially in intensive care units. The present study aimed to investigate the antimicrobial activity of Riparin-B (Rip-B) alone and in association with norfloxacin against multidrug-resistant clinical isolates of A. baumannii. For this, the minimum inhibitory concentrations were determined by the microdilution method. For the evaluation of resistance-modulating activity, MIC values for antibiotics were determined in the presence or absence of subinhibitory concentrations of Rip-B or chlorpromazine (CPZ). The AdeABC-AdeRS efflux system genes from these isolates were detected by PCR. Docking studies were also carried out to evaluate the interaction of Riparin-B and the AdeABC-AdeRS efflux system. The study was conducted from 2017 to 2019. The results showed that Rip-B showed weak intrinsic activity against the strains tested. On the other hand, Rip-B was able to modulate norfloxacin's response against A. baumannii strains that express efflux pump-mediated resistance. Docking studies provided projections of the interaction between Rip-B and EtBr with the AdeB protein, suggesting that Rip-B acts by competitive inhibition with the drug. Results found by in vitro and in silico assays suggest that Rip-B, in combination with norfloxacin, has the potential to treat infections caused by multidrug-resistant A. baumanni with efflux pump resistance.

Plant-food-derived Bioactives in Managing Hypertension: From Current Findings to Upcoming Effective Pharmacotherapies.

A sedentary lifestyle has evoked a high risk of cardiovascular (CV) disease, diabetes, and obesity, all of them with high morbimortality rates and with a common denominator, hypertension. Numerous pharmacological drugs have been used for the treatment of hypertension. However, the side effects associated with the use of existing pharmacological therapies have triggered a demand for plant-based medications. In this connection, the aim of this review was to provide an in-depth analysis of the use of plant-derived bioactives for the effective management of hypertension. Phytoconstituents from leaves, bark, stem, roots, seeds, and fruits of medicinal plants grown in our different regions of the globe have been highly searched. Among them, polyphenols (e.g., flavonoids as quercetin, anthocyanins as cyanidin, tannins as ellagic acid, stilbenes as resveratrol, lignans as honokiol and others as hydroxytyrosol or curcumin), organosulfur compounds (e.g. s-allyl cysteine and allicin), fatty acids (e.g. α-lipoic acid, DHA and oleic acid), alkaloids (e.g. berberine or tetrandrine) and some terpenes have been intensively investigated for the management of hypertension, with effective ability being stated in controlling high blood pressure and related health problems both in vivo and in vitro studies. Some of the activities presented by these bioactive compounds are reducing oxidative stress, renin-angiotensin system control, SIRT1 activation, regulating platelet aggregation and COX activity, anti-atherogenic effects, anti-inflammatory properties, vasorelaxation and other results that translate into the prevention or control of hypertension. The knowledge of these bioactive compounds is important in developing countries where traditional medicine is the majority, but it can also give rise to new approaches in hypertension therapy.

Recent advances in the concept of paraprobiotics: Nutraceutical/functional properties for promoting children health.

Probiotics consumption has been associated with various health promoting benefits, including disease prevention and even treatment by modulating gut microbiota. Contrary to this, probiotics may also overstimulate the immune system, trigger systemic infections, harmful metabolic activities, and promote gene transfer. In children, the fragile immune system and impaired intestinal barrier may boost the occurrence of adverse effects following probiotics' consumption. To overcome these health challenges, the key focus has been shifted toward non-viable probiotics, also called paraprobiotics. Cell wall polysaccharides, peptidoglycans, surface proteins and teichoic acid present on cell's surface are involved in the interaction of paraprobiotics with the host, ultimately providing health benefits. Among other benefits, paraprobiotics possess the ability to regulate innate and adaptive immunity, exert anti-adhesion, anti-biofilm, anti-hypertensive, anti-inflammatory, antioxidant, anti-proliferative, and antagonistic effects against pathogens, while also enhance clinical impact and general safety when administered in children in comparison to probiotics. Clinical evidence have underlined the paraprobiotics impact in children and young infants against atopic dermatitis, respiratory and gastrointestinal infections, in addition to be useful for immunocompromised individuals. Therefore, this review focuses on probiotics-related issues in children's health and also discusses the Lactobacillus and Bifidobacterium spp. qualities for qualifying as paraprobiotics and their role in promoting the children's health.

Current insights into epigenetics, noncoding RNA interactome and clinical pharmacokinetics of dietary polyphenols in cancer chemoprevention.

Several studies have reported the health-beneficial effects of dietary phytochemicals, namely polyphenols, to prevent various diseases, including cancer. Polyphenols, like (-)-epigallocatechin-3-gallate (EGCG) from green tea, curcumin from turmeric, and ellagic acid from pomegranate are known to act by modulating antioxidant, anti-inflammatory and apoptotic signal transduction pathways in the tumor milieu. The evolving literature underscores the role of epigenetic regulation of genes associated with cancer by these polyphenols, primarily via non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long noncoding RNA (lncRNA). However, there is little clarity on the exact role(s) played by these ncRNAs and their interactions with other ncRNAs, or with their protein targets, in response to modulation by these dietary polyphenols. Here, we review ncRNA interactions and functional networks of the complex ncRNA interactome with their targets in preclinical studies along with the role of epigenetics as well as key aspects of pharmacokinetics and phytochemistry of dietary polyphenols. We also summarize the current state of clinical trials with these dietary polyphenols. Taken together, this synthetic review provides insights into the molecular aspects underlying the anticancer chemopreventive effects of dietary polyphenols as well as summarizes data on novel biomarkers modulated by these polyphenols for preventive or therapeutic purposes in various types of cancer.

Chemical Composition and Bioinsecticidal Effects of Thymus zygis L., Salvia officinalis L. and Mentha suaveolens Ehrh. Essential Oils on Medfly Ceratitis capitata and Tomato Leaf Miner Tuta absoluta.

The present work was aimed to study the toxicity of the essential oils of three aromatic and medicinal plants on the tomato leaf miner Tuta absoluta and the Medfly Ceratitis capitata as an alternative to conventional pesticides. We carried out a phytochemical and insecticide study of T. zygis L., S. officinalis L. and M. suaveolens Ehrh. essential oils (EOs) through the study of their chemical composition and their toxicity on C. capitata adults and T. absoluta larvae. The extraction of the EOs by hydrodistillation showed yields of 3.87 ± 0.03, 4.09 ± 0.23 and 4.35 ± 0.11 for T. zygis, S. officinalis L. and M. suaveolens Ehrh., respectively. The identification of the chemical composition of the EOs by GC/MS showed that oxygenated monoterpenes constituted the most abundant group for all the extracted EOs. The major compounds were rather diversified depending on plant species. In fact, the S. officinalis L. EO mainly contained trans-thujone (21.80 %), the M. suaveolens Ehrh. EO mainly contained piperitenone oxide (71.19%), and carvacrol (61.60%) was the main component of the T. zygis L. EO. An insecticidal effect was observed for the three studied EOs on C. capitata adults and T. absoluta larvae. The observed LD50 values were 0.80 µL/mL and 11.04 µL/mL for M. suaveolens and S. officinalis, respectively, on T. absoluta larvae. For C. capitata adults, the obtained LD50 values were 0.9 µL/mL and 11.78 µL/mL for M. suaveolens and T. zygis, respectively. The presented findings could contribute to the development of biopesticides for plants as a component of integrated pest management strategies in citrus and tomato crops.

Pharmacological screening of species from the Lippia genus, content in terpenes and phenylpropanoids, and their vasorelaxing effects on human umbilical artery.

BACKGROUND: Naturally occurring bioactive compounds have a plethora of biological effects. OBJECTIVE: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA). METHODS: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 µg/mL and µM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol). Discussion/Results: The reduction corresponded to approximately 100%, except for limonene (80±1.2 %). When evaluating the concentration of the natural product that promotes 50 % relaxation of the HUA contracted by KCL, EC50 values were: 424.3 µg/mL (EOLa); 468.7±6.7 µg/mL (EOLo); 264.2 ± 8.2 µM (citral); 677.8±5.4 µM (limonene); 186.3±6.4 µM (peryl alcohol); 986.4±7.9 µM (eugenol); and 279.1±4.4 µM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency). CONCLUSION: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Revisiting the Nutritional, Chemical and Biological Potential of Cajanus cajan (L.) Millsp.

The genus Cajanus (Family: Fabaceae) consists of approximately 37 species, and Cajanus cajan (C. cajan) is a significant member of the genus. It is a commercial legume crop widely grown in sub-tropical and semi-arid tropical areas of the world. C. cajan is well known for its folk medicinal uses to treat various disorders, such as toothache, dizziness, diabetes, stomachache, female ailments and chronic infections. These properties have been linked to the presence of several value-added nutritional and bioactive components. Different solvent extracts from C.cajan (leaves, root, stem and seeds) have been evaluated for their phytochemical and biological activities, namely antioxidant, antimicrobial, antidiabetic, neuroprotective, and anti-inflammatory effects. Taken together, and considering the prominent nutraceutical and therapeutic properties of C. cajan, this review article focuses on the important details including ethnomedicinal uses, chemical composition, biological applications and some other medicinal aspects related to C.cajan nutraceutical and pharmacological applications.

In vivo and in silico anti-inflammatory properties of the sesquiterpene valencene.

Valencene (VLN) is a sesquiterpene found in juices and essential oils of citrus species such as Cyperus rotundus. Considering the evidence that this species has anti-inflammatory effects, the present study aims to evaluate the anti-inflammatory activity of VLN in vivo and in silico. Swiss mice (n = 6) were orally treated according to their treatment groups as follows: VLN (10, 100 or 300 mg/kg), negative control (0.9% saline), and positive controls (indomethacin 25 mg/kg or promethazine 6 mg/kg). The anti-inflammatory activity was evaluated in murine models of acute and chronic inflammation. The inhibition of acute inflammation was evaluated in models of paw edema induced by different inflammatory agents (carrageenan, dextran, histamine, and arachidonic acid (AA)) and carrageenan-induced pleurisy and peritonitis. The modulation of chronic inflammation was evaluated in a granuloma model induced cotton pellets implantation. The interaction with inflammatory targets was evaluated in silico using molecular docking analysis. The administration of VLN to challenged mice significantly inhibited paw edema formation with no significant difference between the administered doses. The compound also reduced albumin extravasation, leukocyte recruitment, and the production of myeloperoxidase (MPO), IL-1ß, and TNF-α in both pleural and peritoneal lavages. According to the mathematical-statistical model observed in silico analysis, this compound has favorable energy to interact with the cyclooxygenase enzyme (COX-2) and the histamine 1 (H1) receptor. Finally, animals treated with the sesquiterpene showed a reduction in both granuloma weight and concentration of total proteins in a chronic inflammation model. Given these findings, it is concluded that NLV presents promising pharmacological activity in murine models of acute and chronic inflammation.

Studies of Phytochemicals, Antioxidant, and Antibacterial Activities of Pinus gerardiana and Pinus roxburghii Seed Extracts.

Pine seeds are considered as nonwood forest products (NWFP) with regularly increasing market's demand. They can be eaten in various ways such as roasted or raw. In addition, they are included in various traditional dishes like in cookies, sauces, candies, cakes, breads, and other bakery items and, moreover, for medicinal purposes. GC-MS study is performed to analyze the phytochemical compounds present in the seed extracts of Pinus roxburghii (Chir) and Pinus gerardiana (Chilgoza). In total, 25 compounds were identified each in Chir and Chilgoza. In Chir seeds, abundantly present compounds were 2,4-di-tert-butylphenol (16.6%), followed by ç-Terpinene (9.9%) and cyclohexanol, 4-ethenyl-4-methyl-3-(1-methylethenyl)-, (1à,3à,4á) (9.8%), whereas in Chilgoza seeds, the maximum amount of compound was 1-hexyl-1-nitrocyclohexane (17.3%), followed by phenol, 2,6-bis(1,1-dimethylethyl) (15.4%), and heptadecane, 2-methyl (8.4%). The total phenolic content of Chir seed sample was 1536 ± 4.35 (mg GAE/100 g), whereas in the Chilgoza seed extract was 642.66 ± 2.08 (mg GAE/100 g). The application of RP-HPLC-DAD system revealed that Chir and Chilgoza seeds have maximum quantity of catechin (15.77 ± 0.16 µg/mg and 17.49 ± 0.32 µg/mg, respectively). Both Chir and Chilgoza seed extracts exhibited significant antioxidant (radical scavenging) potential, through H2O2 (618.94 ± 21.45 µg/mL and 575.16 ± 19.88 µg/mL) and DPPH (552.60 ± 13.03 µg/mL and 429.15 ± 3.80 µg/mL) assays, respectively. Additionally, a well-known antibacterial potential was also found in both plants' dichloromethane extracts, with 64 to 256 µg/mL of minimum inhibitory concentrations. As a whole, result shows the importance of both plants as a naturally occurring phytochemical source with significant antibacterial and antioxidant activity.

Poisonous Plants of the Indian Himalaya: An Overview.

Indian Himalayan region (IHR) supports a wide diversity of plants and most of them are known for their medicinal value. Humankind has been using medicinal plants since the inception of civilization. Various types of bioactive compounds are found in plants, which are directly and indirectly beneficial for plants as well as humans. These bioactive compounds are highly useful and being used as a strong source of medicines, pharmaceuticals, agrochemicals, food additives, fragrances, and flavoring agents. Apart from this, several plant species contain some toxic compounds that affect the health of many forms of life as well as cause their death. These plants are known as poisonous plants, because of their toxicity to both humans and animals. Therefore, it is necessary to know in what quantity they should be taken so that it does not have a negative impact on health. Recent studies on poisonous plants have raised awareness among people who are at risk of plant toxicity in different parts of the world. The main aim of this review article is to explore the current knowledge about the poisonous plants of the Indian Himalayas along with the importance of these poisonous plants to treat different ailments. The findings of the present review will be helpful to different pharmaceutical industries, the scientific community and researchers around the world.

Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide.

Andrographolide (ANDRO), a bitter diterpene lactone found in Andrographis paniculata (Burm.f.) Nees, possesses several biological effects such as antioxidant, anti-inflammatory, and organo-protective effects. Scientific reports suggest that it also has neuroprotective capacity in various test systems. The purpose of this review was to synthesize the neuropharmacological properties of ANDRO and highlight the molecular mechanisms of action that highlight these activities. A careful search was done in PubMed and Google Scholar databases using specific keywords. Findings suggest that ANDRO possess neuroprotective, analgesic, and antifatigue effects. Prominent effects were stated on neuro-inflammation, cerebral ischemia, Alzheimer's and Parkinson's diseases, multiple sclerosis, and brain cancer in mice and rats. Furthermore, ANDRO and its derivatives can enhance memory and learning capacity in experimental animals (rats) without causing any toxicity in the brain. Thus, ANDRO may be one of the most promising plant-based psychopharmacological lead compounds for new drug development.

Hyssopus Essential Oil: An Update of Its Phytochemistry, Biological Activities, and Safety Profile.

The genus Hyssopus is widespread in central Asia, East Mediterranean, and Mongolian areas. It has six main species which are used as herbal remedies, such as Hyssopus officinalis which is used as a condiment and flavoring agent in food industry. The other five species are H. ambiguus, H. cuspidatus, H. latilabiatus, H. macranthus, and H. seravschanicus. Its species are used in the treatment of various ailments such as cold, cough, loss of appetite, fungal infection, and spasmodic condition. Its constituents especially essential oils are popularly used as an additive in beverages, foods, and cosmetics. The volatile constituents are used for aroma in the food industry, cosmetic industry, and household products. The important active constituents in its essential oils are ß-pinene, pinocamphone, isopinocamphone, and other terpenoids. Hyssopus genus is also bundled with other secondary metabolites including flavonoids luteolin, quercetin, apigenin, and their glucosides, as well as phenolic compounds including ferulic, p-hydroxy-benzoic acid, protocatechuic acid, chlorogenic, and caffeic acid. Combinedly, the extracts of Hyssopus are reported to have potential antiviral and antifungal activities proven using in vitro studies, whereas in vivo investigations have reported the crucial role of Hyssopus extracts in plasma membrane relaxation, cytotoxic, and sedative effects. This plant is believed to be relatively safe at levels commonly used in foods; nevertheless, more studies are needed to determine the safety profile.

Hesperetin's health potential: moving from preclinical to clinical evidence and bioavailability issues, to upcoming strategies to overcome current limitations.

Flavonoids are common in the plant kingdom and many of them have shown a wide spectrum of bioactive properties. Hesperetin (Hst), the aglycone form of hesperidin, is a great example, and is the most abundant flavonoid found in Citrus plants. This review aims to provide an overview on the in vitro, in vivo and clinical studies reporting the Hst pharmacological effects and to discuss the bioavailability-related issues. Preclinical studies have shown promising effects on cancer, cardiovascular diseases, carbohydrate dysregulation, bone health, and other pathologies. Clinical studies have supported the Hst promissory effects as cardioprotective and neuroprotective agent. However, further well-designed clinical trials are needed to address the other Hst effects observed in preclinical trials, as well as to a more in-depth understanding of its safety profile.

Flavonoids as potential anti-platelet aggregation agents: from biochemistry to health promoting abilities.

Cardiovascular ailments are the number one cause of mortalities throughout the globe with 17.9 million deaths per year. Platelet activation and aggregation play a crucial role in the pathogenesis of arterial diseases, including acute coronary syndrome, acute myocardial infarction, cerebrovascular transient ischemia, unstable angina, among others. Flavonoids-rich plant extracts are gaining interest for treating the heart-related problems due to safe nature of these herbal extracts. Consumption of plant-food-derived bioactives, particularly flavonoids, has shown antithrombotic, and cardiovascular protective effects due to its anti-platelet activity. Preclinical and clinical trials have proven that flavonoid-rich plant extracts are protective against the cardiac ailments through anti-platelet aggregation activity. This review aims to highlight the anti-platelet aggregation potential of flavonoids with a key emphasis on the therapeutic efficacy in humans. The mechanism of flavonoids in preventing and treating cardiovascular diseases is also highlighted based on preclinical and clinical experimental trials. Further studies are the need of time for exploring the exact molecular mechanism of flavonoids as anti-platelet aggregation agents for treating heart-related problems.

Plant-derived alkaloids acting on dengue virus and their vectors: from chemistry to pharmacology.

Dengue is a mosquito-borne viral infection, with its prevention and control depending on effective vector control measures. At present, dengue virus (DENV) is an epidemic in more than 100 countries of Southeast Asia, Africa, Eastern Mediterranean, the Americas and the Western Pacific. Several alkaloids isolated from natural herbs can serve as a reservoir for antiDENV drug development. Traditionally, plant extracts rich in alkaloids are used for the treatment of fever and have also revealed antimicrobial activity against various pathogenic bacteria, fungi and virus. The present narrative review collates the literature-based scenario of alkaloids and derivatives acting on DENV. The mechanism of action of such alkaloids with antiDENV and vector activity is also discussed.

Quercetin Impact in Pancreatic Cancer: An Overview on Its Therapeutic Effects.

Pancreatic cancer (PC) is a lethal malignancy cancer, and its mortality rates have been increasing worldwide. Diagnosis of this cancer is complicated, as it does not often present symptoms, and most patients present an irremediable tumor having a 5-year survival rate after diagnosis. Regarding treatment, many concerns have also been raised, as most tumors are found at advanced stages. At present, anticancer compounds-rich foods have been utilized to control PC. Among such bioactive molecules, flavonoid compounds have shown excellent anticancer abilities, such as quercetin, which has been used as an adjunctive or alternative drug to PC treatment by inhibitory or stimulatory biological mechanisms including autophagy, apoptosis, cell growth reduction or inhibition, EMT, oxidative stress, and enhancing sensitivity to chemotherapy agents. The recognition that this natural product has beneficial effects on cancer treatment has boosted the researchers' interest towards more extensive studies to use herbal medicine for anticancer purposes. In addition, due to the expensive cost and high rate of side effects of anticancer drugs, attempts have been made to use quercetin but also other flavonoids for preventing and treating PC. Based on related studies, it has been found that the quercetin compound has significant effect on cancerous cell lines as well as animal models. Therefore, it can be used as a supplementary drug to treat a variety of cancers, particularly pancreatic cancer. This review is aimed at discussing the therapeutic effects of quercetin by targeting the molecular signaling pathway and identifying antigrowth, cell proliferation, antioxidative stress, EMT, induction of apoptotic, and autophagic features.

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy.

Paclitaxel is a broad-spectrum anticancer compound, which was derived mainly from a medicinal plant, in particular, from the bark of the yew tree Taxus brevifolia Nutt. It is a representative of a class of diterpene taxanes, which are nowadays used as the most common chemotherapeutic agent against many forms of cancer. It possesses scientifically proven anticancer activity against, e.g., ovarian, lung, and breast cancers. The application of this compound is difficult because of limited solubility, recrystalization upon dilution, and cosolvent-induced toxicity. In these cases, nanotechnology and nanoparticles provide certain advantages such as increased drug half-life, lowered toxicity, and specific and selective delivery over free drugs. Nanodrugs possess the capability to buildup in the tissue which might be linked to enhanced permeability and retention as well as enhanced antitumour influence possessing minimal toxicity in normal tissues. This article presents information about paclitaxel, its chemical structure, formulations, mechanism of action, and toxicity. Attention is drawn on nanotechnology, the usefulness of nanoparticles containing paclitaxel, its opportunities, and also future perspective. This review article is aimed at summarizing the current state of continuous pharmaceutical development and employment of nanotechnology in the enhancement of the pharmacokinetic and pharmacodynamic features of paclitaxel as a chemotherapeutic agent.