Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Nutraceuticals in migraine.

Nutraceuticals represent substances derived from food or plants that provide medical or health benefits, and are increasingly sought by patients as a means of treating migraine in a natural, effective, and safe manner as conventional therapies often fail, are expensive, and laden with side effects. This chapter reviews various nutraceutical therapies for migraine including phytomedicines (plant-based therapies), diets for migraine management and vitamin, mineral, and supplement-based treatments for migraine with respect to preclinical and clinical evidence. Reviewed herein are a multitude of nutraceutical options for the treatment of migraine including vitamins (e.g., riboflavin), antioxidants, and plants/phytomedicines: feverfew, butterbur, cannabis, St. John's Wort, Rosa x damascena, and Gingko biloba. Dietary interventions for migraine include low lipid, vegan, ketogenic, and DASH (dietary approaches to stop hypertension). Supplements such as polyunsaturated fatty acids (PUFAs) as well as l-carnitine, pre/probiotics, and melatonin are also discussed. Migraine patients and their caregivers have an armamentarium of nutraceutical options to treat headache. While some therapies such as vitamins harbor stronger evidence with more rigorous studies, patients may also choose dietary therapies that may offer more systemic health benefits while also improving migraine. As cannabis legalization spreads worldwide, care providers must be aware of the limited evidence in migraine. Future studies may explore traditional ancient medicines for migraine at basic science and clinical level, while currently adopted and new nutraceutical treatments may benefit from partnership with industry to engage in larger trials in humans.

Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto.

Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo.

Traditional Herbal Medications Utilized in the Indian Medical System forthe Management of Diabetes: An Updated Review and Clinical Implications.

Phytomedicine, also called botanical medicine, is the practice of using plants to treat disease. Diabetes, for example, has been treated and prevented with herbal medication for a lot longer than Western medicine. Worldwide, diabetes has become a major health concern. The management of diabetes and hyperglycemia, two of the most common public health threats, is far from ideal. When hyperglycemia persists or is not under control, diabetes-related complications, like blindness, lower limb amputations, renal disease, and cardiovascular disease, play a significant role in the morbidity and mortality of the disease. Although chemicals and biochemical agents can assist in managing diabetes, there is currently no complete cure for the disease. Herbal remedies are one of many methods that can be used to treat and prevent diabetes and its subsequent problems. Numerous traditional treatments have been discovered for diabetes as a result of extensive research efforts. However, there are many factors to consider when deciding which herbs to use, such as the patient's financial status, the presence or absence of co-morbidities, and the accessibility, cost-effectiveness, and safety profile of the herbs. This article focuses on the use of herbal and natural remedies in the treatment and prevention of diabetes, the mechanisms by which these remedies lower blood glucose levels, and the specific herbal items now utilized in the management of diabetes.

Boswellia carterii oleoresin extracts induce caspase-mediated apoptosis and G1 cell cycle arrest in human leukaemia subtypes.

Background: Leukemias are a common cancer in adults and children. While existing treatments are effective, they are associated with severe side-effects compounded by the emergence of drug resistance. This necessitates the need to develop new drugs and phytopharmaceuticals offer a largely untapped source. Oleoresins produced by plants in the genus Boswellia have been used for centuries in traditional medicine and recent work suggests they may exhibit anti-cancer activity. However, the underlying mechanisms remain unclear and most existing research focusses on Boswellia serrata; just one of many species in the Boswellia genus. To address these limitations, we elucidated the anti-cancer potential and associated mechanisms of action of Boswellia carterii. Methods: A methanolic solvent extraction method was optimised. The effect of methanolic extracts of B. carterii on leukaemia (K562, MOLT-4 and CCRF-CEM) and normal (PBMC) cell line viability was assessed using MTT assay and flow cytometry. Cell morphology, apoptosis (Annexin-V/propidium iodide), mitochondrial membrane potential (Rhodamine-123) and the cell cycle (propidium iodide) were evaluated using flow cytometry. Regulatory protein expression was quantified using Western Blot. Results: Methanolic extracts of B. carterii oleoresin reduced the viability of K562, MOLT-4 and CCRF-CEM cell lines with selectivity indexes of between 1.75 and 2.68. Extracts increased the proportion of cells in late apoptosis by 285.4% ± 51.6%. Mitochondrial membrane potential was decreased by 41% ± 2% and the expression of cleaved caspase-3, -7, and -9 was increased by 5.7, 3.3, and 1.5-fold respectively. Extracts increased the proportion of cells in subG1 and G1 phase by 867.8% ± 122.9% and 14.0 ± 5.5 and decreased those in S phase and G2/M by 63.4% ± 2.0% and 57.6% ± 5.3%. Expression of CDK2, CDK6, cyclin D1, and cyclin D3 were decreased by 2.8, 4.9, 3.9, and 2.5-fold. Conclusion: We are the first to report that methanolic extracts of B. carterii are selectively cytotoxic against three leukemia cell lines. Cytotoxic mechanisms likely include activation of the intrinsic apoptotic pathway and cell cycle arrest through downregulation of CDK2, CDK6, cyclin D1, and cyclin D3. Our findings suggest that B. carterii may be an important source of novel chemotherapeutic drugs and justifies further investigation.

Essential Oils in Cervical Cancer: Narrative Review on Current Insights and Future Prospects.

Cervical cancer is a prevalent and often devastating disease affecting women worldwide. Traditional treatment modalities such as surgery, chemotherapy, and radiation therapy have significantly improved survival rates, but they are often accompanied by side effects and challenges that can impact a patient's quality of life. In recent years, the integration of essential oils into the management of cervical cancer has gained attention. This review provides an in-depth exploration of the role of various essential oils in cervical cancer, offering insights into their potential benefits and the existing body of research. The review also delves into future directions and challenges in this emerging field, emphasizing promising research areas and advanced delivery systems. The encapsulation of essential oils with solid lipid nanoparticles, nanoemulsification of essential oils, or the combination of essential oils with conventional treatments showed promising results by increasing the anticancer properties of essential oils. As the use of essential oils in cervical cancer treatment or management evolves, this review aims to provide a comprehensive perspective, balancing the potential of these natural remedies with the challenges and considerations that need to be addressed.

Current Advances in Nanotechnology-Mediated Delivery of Herbal and Plant-Derived Medicines.

Phytomedicine has been used by humans since ancient times to treat a variety of diseases. However, herbal medicines face significant challenges, including poor water and lipid solubility and instability, which lead to low bioavailability and insufficient therapeutic efficacy. Recently, it has been shown that nanotechnology-based drug delivery systems are appropriate to overcome the above-mentioned limitations. The present review study first discusses herbal medicines and the challenges involved in the formulation of these drugs. The different types of nano-based drug delivery systems used in herbal delivery and their potential to improve therapeutic efficacy are summarized, and common techniques for preparing nanocarriers used in herbal drug delivery are also discussed. Finally, a list of nanophyto medicines that have entered clinical trials since 2010, as well as those that the FDA has approved, is presented.

Analysis of complementarities between nanomedicine and phytodrugs for the treatment of malarial infection.

The use of nanocarriers in medicine, so-called nanomedicine, is one of the most innovative strategies for targeting drugs at the action site and increasing their activity index and effectiveness. Phytomedicine is the oldest traditional method used to treat human diseases and solve health problems. The recent literature on the treatment of malaria infections using nanodelivery systems and phytodrugs or supplements has been analyzed. For the first time, in the present review, a careful look at the considerable potential of nanomedicine in promoting phytotherapeutic efficacy was done, and its key role in addressing a translation through a significant reduction of the current burden of malaria in many parts of the world has been underlined.

Plants hide an incredible treasure chest of beneficial substances within them. These natural substances have a wide range of beneficial applications for human health, from nutrition to personal care, including the treatment of diseases such as malaria. However, to exploit the full potential of these substances, an innovative approach is needed, and nanomedicine promises that. Nanomedicine involves the use of nanosystems, incredibly small systems, invisible to the naked eye, but their impact is enormous. Thus, bioactive compounds in plants that may have beneficial effects on human health can be placed within these nanosystems to improve their effectiveness. This synergy between nature and nanotechnology offers new opportunities to improve health and well-being, demonstrating how valuable science and technology are in exploring the natural world. After examining the key advantages of nanosystems, this review focuses on some of the earliest antimalarials used and then looks at newer and more promising ones, starting with quinine, extracted from Cinchona bark; moving to the discovery of artemisinin, obtained from Artemisia annua and its derivatives; and ending with an analysis of alternative natural molecules with antimalarial activity. This review examines how nanomedicine can make natural plant-based treatments more effective in fighting malaria. This could help reduce the impact of malaria in many places around the world.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Polyamines and hormesis: Making sense of a dose response dichotomy.

The diverse biological effects of polyamines (putrescine, spermidine and spermine) were reviewed in the context of hormesis in an integrative manner for the first time. The findings illustrate that each of these polyamines commonly induces hormetic dose responses in a wide range of biological models and types of cells for multiple endpoints in numerous plant species and animal models. Plant research emphasized preconditioning experimental studies in which the respective polyamines conferred some protection against the damaging effects of a broad range of environmental stressors such as drought, salinity, cold/heat, heavy metals and UV-damage in an hormetic manner. Polyamine-based animal hormesis studies emphasized biomedical endpoints such as longevity and neuroprotection. These findings have important biological and biomedical implications and should guide experimental designs of low dose investigations.

Integrated traditional herbal medicine in the treatment of gastrointestinal disorder: the pattern of use and the knowledge of safety among the Eastern Region Saudi population.

BACKGROUND: Herbal medicine is commonly integrated with conventional medicine in Saudi Arabia, especially for the management of digestive disorders. However, the majority of Saudis use herbal remedies without prior consultation with a physician, which raises concerns about their appropriate and safe use. The aim of this study was to assess the level of awareness among the Saudi population regarding the proper utilization and potential adverse effects of frequently used herbs for the treatment of gastrointestinal (GI) diseases. METHODS: A cross-sectional survey was conducted in Saudi Arabia from January to March 2021. An electronic self-administered questionnaire was distributed. RESULTS: A total of 543 participants from different age groups, educational levels, and cities across Saudi Arabia completed the study questionnaire. The most commonly used herbs at home by the participants were: myrrh, parsley, black seed, chamomile, mint, anise, clove, and green tea. 57.7% of the participants perceived herbs as safer than conventional medicines; 27.3% reported that using herbal remedies over conventional medicine was a family tradition, and 21.4% used herbs because they were cheaper than conventional medicines. CONCLUSION: Herbal remedies, including myrrh, parsley, blackseed, chamomile, mint, and anise, are commonly employed for the treatment of gastrointestinal disorders in Saudi Arabia. However, the knowledge level of participants regarding potential side effects and drug-herb interactions was found to be deficient. As such, there is a pressing need for educational campaigns and community awareness programs to elucidate the proper usage of herbal remedies and to caution against their potential adverse effects.

In Vivo Efficacy of Curcumin and Curcumin Nanoparticle in Trypanosoma congolense, Broden 1904 (Kinetoplastea: Trypanosomatidae)-Infected Mice.

Curcumin (CUR) is known for its wide folkloric effects on various infections; however, its solubility status has remained a hindrance to its bioavailability in the host. This study evaluated the comparative effects of CUR and CUR-nanoparticle in vitro on T. congolense, T. b. brucei, and T. evansi. Additionally, CUR and CUR-nanoparticle anti-Trypanosoma efficacy were assessed in vivo against T. congolense. All the CUR-nanoparticles were two folds more effective on the T. congolense as compared to CUR in vitro, with recorded efficacy of 3.67 ± 0.31; 7.61 ± 1.22; and 6.40 ± 3.07 µM, while the CUR-nanoparticles efficacy was 1.56 ± 0.50; 28.16 ± 9.43 and 13.12 ± 0.13 µM on T. congolense, T. b. brucei, and T. evansi, respectively. Both CUR and CUR-nanoparticles displayed moderate efficacy orally. The efficacy of CUR and CUR-nanoparticles in vivo was influenced by solubility, presence of food, and treatment period. CUR-treated mice were not cured of the infection; however, the survival rate of the orally treated mice was significantly prolonged as compared with intraperitoneal-treated mice. CUR-nanoparticles resulted in significant suppression of parasitemia even though relapsed was observed. In conclusion, CUR and CUR-nanoparticles possess moderate efficacy orally on the trypanosomes as compared to the intraperitoneal treatment.

Moringa induces its beneficial effect via hormesis.

Moringa oleifera, a traditional Indian herb, is widely known for its capacity to induce antioxidant, anti-inflammatory and other chemoprotective effects in a broad range of biomedical models. These perspectives have led to an extensive number of studies using various moringa extracts to evaluate its capacity to protect biological systems from oxidative stress and to explore whether it could be used to slow the onset of numerous age-related conditions and diseases. Moringa extracts have also been applied to prevent damage to plants from oxidative and saline stresses, following hormetic dose­response patterns. The present paper provides the first integrated and mechanistically based assessment showing that moringa extracts commonly induce hormetic dose responses and that many, perhaps most, of the beneficial effects of moringa are due to its capacity to act as an hormetic agent.

The effects of Quercetin supplementation on cardiometabolic outcomes: An umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Quercetin is a bioactive flavonoid, but the effect of it on cardiometabolic factors has remained uncertain and previous findings from meta-analyses have been controversial. OBJECTIVE: To provide an overview of the effects of Quercetin on cardiometabolic factors based on meta-analyses of randomized controlled trials (RCTs). METHOD: MEDLINE, SciVerse Scopus, and Clarivate Analytics Web of Science databases were searched to identify eligible publications. As part of the umbrella review, we summarized pooled estimates, 95% CIs, heterogeneity, and publication bias. A GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach was used to rate the certainty of evidence. RESULTS: Five meta-analyses including 18 eligible RCTs plus 5 RCTs that were not included in previous meta-analyses were found. The results indicated Quercetin does not affect diastolic blood pressure (DBP), lipid profile, inflammation, anthropometric indices, fasting plasma glucose (FBG), and homeostatic model assessment for insulin resistance (HOMA-IR). However, Quercetin supplementation could significantly reduce systolic blood pressure (SBP) (weighted mean difference (WMD): -1.9, 95% CI = -3.2 to -0.6, I2 = 88.3%) and insulin level (WMD: -1.07, 95% CI = -1.9 to -0.1, I2 = 75.0%). The certainty of evidence ranged from very low to moderate. CONCLUSION: Quercetin supplementation has reducing effects on SBP and insulin levels but not other cardiometabolic parameters. More high-quality trials with longer follow-up durations may be required to obtain a more robust conclusion.

Helicobacter pylori in the post-antibiotics era: from virulence factors to new drug targets and therapeutic agents.

Helicobacter pylori is considered one of the most prevalent human pathogenic microbes globally. It is the main cause of a number of gastrointestinal ailments, including peptic and duodenal ulcers, and gastric tumors with high mortality rates. Thus, eradication of H. pylori is necessary to prevent gastric cancer. Still, the rise in antibiotic resistance is the most important challenge for eradication strategies. Better consideration of H. pylori virulence factors, pathogenesis, and resistance is required for better eradication rates and, thus, prevention of gastrointestinal malignancy. This article is aimed to show the role of virulence factors of H. pylori. Some are involved in its survival in the harsh environment of the human gastric lumen, and others are related to pathogenesis and the infection process. Furthermore, this work has highlighted the recent advancement in H. pylori treatment, as well as antibiotic resistance as a main challenge in H. pylori eradication. Also, we tried to provide an updated summary of the evolving H. pylori control strategies and the potential alternative drugs to fight this lethal resistant pathogen. Recent studies have focused on evaluating the efficacy of alternative regimens (such as sequential, hybrid, concomitant treatment, vonoprazan (VPZ)-based triple therapy, high-dose PPI-amoxicillin dual therapy, probiotics augmented triple therapy, or in combination with BQT) in the effective eradication of H. pylori. Thus, innovating new anti-H. pylori drugs and establishing H. pylori databanks are upcoming necessities in the near future.

Nanotechnology-Based Drug Delivery Approaches of Mangiferin: Promises, Reality and Challenges in Cancer Chemotherapy.

Mangiferin (MGF), a xanthone derived from Mangifera indica L., initially employed as a nutraceutical, is now being explored extensively for its anticancer potential. Scientists across the globe have explored this bioactive for managing a variety of cancers using validated in vitro and in vivo models. The in vitro anticancer potential of this biomolecule on well-established breast cancer cell lines such as MDA-MB-23, BEAS-2B cells and MCF-7 is closer to many approved synthetic anticancer agents. However, the solubility and bioavailability of this xanthone are the main challenges, and its oral bioavailability is reported to be less than 2%, and its aqueous solubility is also 0.111 mg/mL. Nano-drug delivery systems have attempted to deliver the drugs at the desired site at a desired rate in desired amounts. Many researchers have explored various nanotechnology-based approaches to provide effective and safe delivery of mangiferin for cancer therapy. Nanoparticles were used as carriers to encapsulate mangiferin, protecting it from degradation and facilitating its delivery to cancer cells. They have attempted to enhance the bioavailability, safety and efficacy of this very bioactive using drug delivery approaches. The present review focuses on the origin and structure elucidation of mangiferin and its derivatives and the benefits of this bioactive. The review also offers insight into the delivery-related challenges of mangiferin and its applications in nanosized forms against cancer. The use of a relatively new deep-learning approach to solve the pharmacokinetic issues of this bioactive has also been discussed. The review also critically analyzes the future hope for mangiferin as a therapeutic agent for cancer management.

Tanshinone IIA targeting cell signaling pathways: a plausible paradigm for cancer therapy.

Natural compounds originating from plants offer a wide range of pharmacological potential and have traditionally been used to treat a wide range of diseases including cancer. Tanshinone IIA (Tan IIA), a bioactive molecule found in the roots of the Traditional Chinese Medicine (TCM) herb Salvia miltiorrhiza, has been shown to have remarkable anticancer properties through several mechanisms, such as inhibition of tumor cell growth and proliferation, metastasis, invasion, and angiogenesis, as well as induction of apoptosis and autophagy. It has demonstrated excellent anticancer efficacy against cell lines from breast, cervical, colorectal, gastric, lung, and prostate cancer by modulating multiple signaling pathways including PI3K/Akt, JAK/STAT, IGF-1R, and Bcl-2-Caspase pathways. This review focuses on the role of Tan IIA in the treatment of various cancers, as well as the underlying molecular mechanisms.

Recent advance in phytonanomedicine and mineral nanomedicine delivery system of the treatment for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy caused by excessive proliferation of myeloblasts. Classical chemotherapies and cell transplantation therapies have remarkable efficacy in AML treatment; however, 30-40% of patients relapsed or had refractory disease. The resistance of AML is closely related to its inherent cytogenetics or various gene mutations. Recently, phytonanomedicine are found to be effective against resistant AML cells and have become a research focus for nanotechnology development to improve their properties, such as increasing solubility, improving absorption, enhancing bioavailability, and maintaining sustained release and targeting. These novel phytonanomedicine and mineral nanomedicine, including nanocrystals, nanoemulsion, nanoparticles, nanoliposome, and nanomicelles, offer many advantages, such as flexible dosages or forms, multiple routes of administration, and curative effects. Therefore, we reviewed the application and progress of phytomedicine in AML treatment and discussed the limitations and future prospects. This review may provide a solid reference to guide future research on AML treatment.