Plant-derived natural compounds in the treatment of arsenic-induced toxicity

Arsenic toxicity,imposed mainly by arsenic-contaminated groundwater,is considered a critical threat to global communal health,as there is no specific and proven conventional therapy for chronic arsenic toxicity,i.e.,arsenicosis,which is an insidious global public health menace affecting 50 countries.Alternative options should,therefore,be explored for the mitigation of arsenicosis.Literature survey reveals several natural compounds from plants possess significant protective efficacy against arsenic toxicity in chiefly preclinical and few clinical investigations.The studies on the ameliorative effects of plant-derived natural compounds against arsenic toxicity published in the last 25 years are collated.Forty-eight plant-based natural compounds possess alleviative effects on experimental arsenic-induced toxicity in animals,six of which have been reported to be clinically effective in humans.A potential nutraceutical or therapeutic candidate against arsenicosis for humans may thus be developed with the help of recent advancements in research in this area,along with the currently available treatments.

Medical plant extracts and natural compounds with a hepatoprotective effect against damage caused by antitubercular drugs: A review

Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.

Natural compounds and extracts from Mexican medicinal plants with anti-leishmaniasis activity: An update

Leishmaniasis is considered as an emerging, uncontrolled disease and is endemic in 98 countries. Annually, about 2 million cases of cutaneous and 500000 cases of visceraltype leishmaniasis are recorded and 60000 persons died from the disease. In Mexico,cutaneous leishmaniasis is known as chiclero's ulcer and is reported in 22 states, it is considered as a health problem. For its treatment, pentavalent antimonial drugs are administered. These drugs cause severe side effects, are costly. Drug-resistant cases have been reported and have been developing for over 70 years. One alternative to the drugs that are currently available is to find active molecules in medicinal plants. Dihydrocorynantheine, corynantheine and corynantheidine are active against Leishmania major,while harmane, pleiocarpin, buchtienin, luteolin and quercetin are active against Leishmania donovani. In Mexico, about 20 medicinal plants have been evaluated against Leishmania mexicana, among which the most active are Tridax procumbens, Lonchocarpus xuul and Pentalinon andrieuxii. From these plants, active compounds with IC_(50)≤30 mg/mL or m M have been isolated, such as 3(S)-16,17-didehydrofalcarinol or Oxylipin, cholestra-4,20,24-trien-3-one or pentalinosterol, 24-methylcholest-4-24(28)-dien-3-one, cholest-4-en-3-one, 6,7-dihydroneridie-none, neridienone, cholest-5,20,24-trien-3β-ol, and isocordoin. Today, only pentalinonsterol has been synthesized and assayed in the visceral leishmaniasis experimental model using BALB/c mice infected with Leishmania donovani. Liposome formulation of this compound administered by intravenous route at 2.5 mg/kg showed a significant reduction of parasite load in mouse liver and spleen.

Natural Compound Curcumin—a Channel Potentiator Rather Than a Corrector of the Defective Intracellular Processing of △F508 Mutant Cystic Fibrosis Transmembrane Conductance Regulator

Cystic fibrosis（CF） is a severe genetic disease caused by the gene mutation of the cystic fibrosis transmembrane conductance regulator（CFTR） chloride channel. The most common point mutation AF508, which leads to impaired intracellular processing and channel gating of CFTR, appears in about 90% CF patients. The natural compound curcumin was reported to correct the processing defect of AF508-CFTR and proposed as a potential therapeutic drug to cure CF. In the present study, we analyzed the effect of curcumin on AF508-CFTR and demonstrated that curcumin can restore the impaired chloride conductance of AF508 mutant CFTR. The activity is rapid, reversible and cAMP-dependent. However, we couldn＇t reproduce the previously reported correction of the defective membrane trafficking of AF508-CFTR by curcumin. Therefore, curcumin may not be a superior lead compound for developing anti-CF drugs.

Natural compounds may contribute in preventing SARS-CoV-2 infection:a narrative review

Coronavirus pandemic infection is the most important health issue worldwide.Coronavirus disease 2019 is a contagious disease characterized by severe acute respiratory syndrome coronavirus 2.To date,excluding the possibility of vaccination,against SARS-CoV-2 infection it is possible to act only with supportive care and non-virus-specific treatments in order to improve the patient’s symptoms.Pharmaceutical industry is investigating effects of medicinal plants,phytochemical extracts and aromatic herbs to find out natural substances which may act as antiviral drugs.Several studies have revealed how these substances may interfere with the viral life cycle,viral entry,replication,assembly or discharge,as well as virus-specific host targets or stimulating the host immune system,reducing oxidative stress and inflammatory response.A natural compound can be used as a prophylaxis by people professionally exposed to the risk of contagion and/or positive patients not in intensive care.The aim of this paper is to perform a narrative review of current literature in order to summarize the most studied natural compounds and their modes of action.

Possible protective action of neurotrophic factors and natural compounds against common neurodegenerative diseases

It has been suggested that altered levels/function of brain-derived neurotrophic factor （BDNF） play a role in the pathophysiology of neurodegenerative diseases including Alzheimer＇s disease. BDNF positively contributes to neural survival and synapse maintenance via stimulating its high affinity receptor TrkB, making upregulation of BDNF and/or activation of BDNF-related intracellnlar signaling an attractive approach to treating neurodegenerative diseases. In this short review, I briefly introduce small natural compounds such as flavonoids that successfully increase activation of the BDNF system and discuss their beneficial effects against neurodegeneration.

Natural Compound Curcumin Corrects the Gating Defect of G551DMutant Cystic Fibrosis Transmembrane Conductance Regulator

In the present study, we identified the natural compound curcumin to be an effective G551D-CFTR activator by cell-based fluorescent assay and electrophysiological measurement. We demonstrated that curcumin can restore the impaired chloride conductance of G551D mutant CFTR. The activity is rapid, reversible, and cAMP-dependent. Our study identified a new natural lead compound for the pharmacological therapy of cystic fibrosis caused by G551D mutation of CFTR.

Natural Compound Formula RM88 Significantly Reduces Blood Alcohol Concentration in Humans

There is extensive worldwide use for the social consumption of alcohol. Abuse of alcohol causes substantial personal, psychological and medical health issues. In addition, there are significant national economic costs from lost productivity. However, there are limited pharmaceutical drugs for the treatment of alcohol overuse. Historically, many cultures have used herbs and other natural compounds to reduce problematic alcohol induced behaviour but the evidence is anecdotal. This study investigated if a natural compound formula (RM88) that was developed could reduce blood alcohol concentration (BAC) in a controlled case series. Thirteen subjects (5 males, 8 females, age range 18 to 85 years) completed 16 paired sessions of alcohol only versus RM88 with alcohol. Subjects consumed one to three standard drinks of beer, wine or spirits (14.7 to 29.4 gm alcohol). Measurements were made by a fuel cell breathalyzer for a period of 90 minutes. Summated BAC showed a reduction in 94% (15/16) of paired test sessions (BAC reduction range 23% - 79%, mean 50.9% ± 16.5%, p = 0.0005). Data normalized to 20 gm alcohol (two standard drinks) showed a significance of p = 0.00026. One subject on prednisone and hydroxychloroquine drugs had increased BAC from RM88. The average reductions of BAC for the beverages were spirits 34% (n = 3), beer 36% (n = 3), and wine 52% (n = 10). RM88 showed that this combination of natural compounds was very effective in reducing maximal peak concentrations of alcohol.

Research Progress on Toxicity of Natural Compounds

There are many active substances in natural resources.After years of research,researchers at home and abroad have extracted active compounds and proved that these compounds have low toxicity and high efficiency,but the toxicity of these compounds cannot be ignored.In this paper,the research progress on the toxicity of compounds isolated from various natural substances is reviewed,which provides a reference for the further development and rational utilization of natural compounds.

A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer

Objective: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas(HNSC). Methods: Gene expression data of HNSC samples and peripheral blood mononuclear cells(PBMCs) of HNSC patients were collected from Gene Expression Omnibus(GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres(DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. Results: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expressions of all 110 commonly DEGs were altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. Conclusions: This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

Interactions of naturally occurring compounds with antimicrobials

Antibiotics are among the most often used medications in human healthcare and agriculture.Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts.To solve these problems,new solutions in antibacterial therapy are needed.The use of natural products in medicine has been known for centuries.Some of them have antibacterial activity,hence the idea to combine their activity with commercial antibiotics to reduce the latter's use.This review presents collected information on natural compounds(terpenes,alkaloids,flavonoids,tannins,sulfoxides,and mycotoxins),of which various drug interactions have been observed.Many of the indicated compounds show synergistic or additive interactions with antibiotics,which suggests their potential for use in antibacterial therapy,reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance.Unfortunately,there are also compounds which interact antagonistically,potentially hindering the therapy of bacterial infection.Depending on its mechanism of action,each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.

Recent advances in natural compounds inducing non-apoptotic cell death for anticancer drug resistance

The induction of cell death is recognized as a potent strategy for cancer treatment.Apoptosis is an extensively studied form of cell death,and multiple anticancer drugs exert their therapeutic effects by inducing it.Nonetheless,apoptosis evasion is a hallmark of cancer,rendering cancer cells resistant to chemotherapy drugs.Consequently,there is a growing interest in exploring novel non-apoptotic forms of cell death,such as ferroptosis,necroptosis,pyroptosis,and paraptosis.Natural compounds with anticancer properties have garnered significant attention due to their advantages,including a reduced risk of drug resistance.Over the past two decades,numerous natural compounds have been discovered to exert anticancer and anti-resistance effects by triggering these four non-apoptotic cell death mechanisms.This review primarily focuses on these four non-apoptotic cell death mechanisms and their recent advancements in overcoming drug resistance in cancer treatment.Meanwhile,it highlights the role of natural compounds in effectively addressing cancer drug resistance through the induction of these forms of non-apoptoticcell death.

Bioactive natural compounds against human coronaviruses: a review and perspective

Coronaviruses(CoVs),a family of enveloped positive-sense RNA viruses,are characterized by club-like spikes that project from their surface,unusually large RNA genome,and unique replication capability.Co Vs are known to cause various potentially lethal human respiratory infectious diseases,such as severe acute respiratory syndrome(SARS),Middle East respiratory syndrome(MERS),and the very recent coronavirus disease 2019(COVID-19)outbreak.Unfortunately,neither drug nor vaccine has yet been approved to date to prevent and treat these diseases caused by CoVs.Therefore,effective prevention and treatment medications against human coronavirus are in urgent need.In the past decades,many natural compounds have been reported to possess multiple biological activities,including antiviral properties.In this article,we provided a comprehensive review on the natural compounds that interfere with the life cycles of SARS and MERS,and discussed their potential use for the treatment of COVID-19.

Natural compounds modulate the autophagy with potential implication of stroke

Stroke is considered a leading cause of mortality and neurological disability,which puts a huge burden on individuals and the community.To date,effective therapy for stroke has been limited by its complex pathological mechanisms.Autophagy refers to an intracellular degrading process with the involvement of lysosomes.Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents.Increasing evidence support that autophagy protects neuronal cells from ischemic injury.However,under certain circumstances,autophagy activation induces cell death and aggravates ischemic brain injury.Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke.In the present work,we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

Modulation of signal transduction pathways by natural compounds in cancer

Cancer is generally regarded as the result of abnormal growth of cells. According to World Health Organization, cancer is the leading cause of mortality worldwide. Mother nature provides a large source of bioactive compounds with excellent therapeutic efficacy. Numerous phytochemicals from nature have been investigated for anticancer properties. In this review article, we discuss several natural compounds, which have shown anti-cancer activity. Natural compounds induce cell cycle arrest, activate intrinsic and extrinsic apoptosis pathways, generate Reactive Oxygen Species(ROS), and down-regulate activated signaling pathways, resulting in inhibition of cell proliferation, progression and metastasis of cancer. Several preclinical studies have suggested that natural compounds can also increase the sensitivity of resistant cancers to available chemotherapy agents. Furthermore, combining FDA approved anti-cancer drugs with natural compounds results in improved efficacy. On the basis of these exciting outcomes of natural compounds against several cancer types, several agents have already advanced to clinical trials. In conclusion, preclinical results and clinical outcomes against cancer suggest promising anticancer efficacy of agents from natural sources.

A critical review on natural compounds interacting with the plant plasma membrane H^(+)-ATPase and their potential as biologicals in agriculture

The plant plasma membrane(PM)H^(+)-ATPase is an essential enzyme controlling plant growth and development.It is an important factor in response to abiotic and biotic stresses and is subject to tight regulation.We are in demand for new sustainable natural growth regulators and as a key enzyme for regulation of transport into the plant cell the PM H^(+)-ATPase is a potential target for these.In this review,we have evaluated the known non-protein natural compounds with regulatory effects on the PM H^(+)-ATPase,focusing on their mechanism of action and their potential as biologicals/growth regulators in plant production of future sustainable agriculture.

Neuroglobin and neuroprotection:the role of natural and synthetic compounds in neuroglobin pharmacological induction

Neuroglobin(Ngb)is a 17 kDa monomeric hexa-coordinated heme protein belonging to the globin family.Ngb is mainly expressed in neurons of the central and peripheral nervous system,although moderate levels of Ngb have been detected in non-nervous tissues.In the past decade,Ngb has been studied for its neuroprotective role in a large number of neurological disorders such as Alzheimer’s disease,Huntington’s disease,brain ischemia and hypoxia.This review discusses and summarizes the natural compounds and the small synthetic molecules capable of modulating Ngb expression that exhibits a protective role against various neurodegenerative diseases.

Effects of natural compounds in treatment and prevention ofhepatotoxicity and hepatocellular carcinoma

Liver diseases are most common disorders in the world and characterized by rapid changes from steatosis to chronic hepatitis,fi brosis,cirrhosis,and hepatocellular carcinoma(HCC).Natural products that attained great attention is to be used in the prevention and treatment of multiple diseases in humans.Several researches have been reported numerous natural and phytochemical compounds that may counteract or prevent the hepatic injury and primary liver cancer.The conservative treatment of liver toxicity and HCC may face awkward challenges in chemotherapy such as therapeutic failure or drug resistance.Accordingly,there is an actual need for safe and effective therapeutic and preventive modalities for liver disorders.The present review aims to focus on the potential protective and therapeutic effects of natural compounds in the prevention and treatment of hepatotoxicity and HCC.It also demonstrates the mechanism of the natural products in enzymatic regulation of antioxidants and its role in apoptosis and proliferation of cancerous lesions of hepatocytes.Accordingly,it highlights the promising role of natural bioactive compounds and provides the rational for further transitional researches,and emphasize on the scientifi c validation of natural compounds for therapeutic portfolio for clinical use in liver diseases.

The Natural Law of Transition of a Charged Particle into a Compound State under the Action of an Electroscalar Field

This article is the continuation of article [1] where the experimental facts of observation of the electroscalar radiation in the spectrum of the Sun have been presented [2]. This radiation comes into the world having a long wavelength, being longitudinal and extraordinarily penetrating. In accordance with the principle of least action, the Lagrangian of the electroscalar field and the tensor of energy-moment are determined using the variation the potential and coordinates. The equation of motion the charged particle in electroscalar field is determined and the energy of particle has the negative sign with respect to the mechanical energy of particle and the energy of electromagnetic field. So, this is decreasing the electrical potential of particle during the propagation. The electroscalar energy of charged particle and field’s force acting on the particle during their motion change the particle’s electrical status which, in its turn, may trigger the transition of the particle into a compound state during interaction with any object. Due to the continuity this process can lead the particle to the state which enters into a compound state with a negative energy for a different particle’s velocity. This state is the physical vacuum’s state. Analysis of the solar spectrum demonstrates that scattering and absorption of electroscalar wave go on the cavities of solids. The spreading out of electroscalar field obeys to the law of plane wave and the transfer the energy and information can occur in vacuum and any medium.

Assessment on facile Diels-Alder approach of α-pyrone and terpenoquinone for the expedient synthesis of various natural scaffolds

The development of highly facile synthetic procedures for the expedient synthesis of complex natural molecules is always in demand.As this aspect,the Diels-Alder reaction(DAR)has a versatile approach to the synthesis of complex natural compounds and highly regio-/stereoselcetive heterocyclic scaffolds.Additionally,α-pyrone and terpeno-quinone are two versatile key intermediates that are prevalent in various bioactive natural compounds for instance,(±)-crinine,(±)-joubertinamine,(±)-pancratistatin,(−)-cyclozonarone,and 8-ephipuupehedione,etc.Hence,the current review summarizes the Diels-Alder reaction application ofα-pyrone and terpenoquinone to the construc-tive synthesis of various natural products over the past two decades(2001-2021).Equally,it serves as a stencil for the invention and development of new synthetic strategies for high-complex molecular structured natural and heterocy-clic molecules.