Natural sources, biosynthesis, biological functions, and molecular mechanisms of shikimic acid and its derivatives

Shikimic acid is a hydroaromatic compound possessing critical biological properties,such as antibacterial and antiviral activity.This review mainly focused on shikimic acid and its derivatives.We first briefly introduced the sources of shikimic acid and its derivatives and discussed their biosynthesis.Several in vitro and in vivo studies indicate that shikimic acid and its derivatives exhibit diverse bioactivities,such as antioxidant,antiviral,anti-inflammatory,antibacterial,hypolipidemic,bone protective,skin protective,neuroprotective,and antidiabetic activities.We mainly focused on the related molecular mechanisms.Overall,the wide range of bioactivities of shikimic acid and its derivatives indicate that a more detailed exploration of their potential for the prevention and treatment of certain diseases is warranted.

Mosquito larvicidal and ovicidal properties of Eclipta alba(L.) Hassk(Asteraceae) against chikungunya vector,Aedes aegypti(Linn.)(Diptera:Culicidae)

Objective:The present study deals with the investigation of larvicidal and ovicidal activities of benzene,hexane,ethyl acetate,methanol and chloroform leaf extract of Eclipta alba（E.alba） against dengue vector,Aedes aegypti（Ae.Aegypti）.Methods:Twenty five earlyⅢinstar larvae of Ae.aegypti was exposed to various concentrations（50-300 ppm） and was assayed in the laboratory by using the protocol of WHO 2005;the 24 h LC50 values of the E.alba leaf extract was determined by Probit analysis.For ovicidal activity,slightly modified method of Su and Mulla was performed.The ovicidal activity was determined against Ae.aegypti to various concentrations ranging from 100-350 ppm under the laboratory conditions.The egg hatch rates were assessed 48 h post treatment.Results:The LC50 values of benzene,hexane,ethyl acetate,methanol and chloroform extract of E.alba against early third instar larvae of Ae.aegypti were 151.38,165.10, 154.88,127.64 and 146.28 ppm,respectively.Maximum larvicidal activity was observed in the methanol extract followed by chloroform,benzene,ethyl acetate and hexane extract.No mortality was observed in control.Among five solvent tested the methanol extract was found to be most effective for ovicidal activity against Ae.aegypti.The methanol extracts exerted 100%mortality （zero hatchability） at 300 ppm.Conclusions:From the results it can be concluded the crude extract of E.alba was an excellent potential for controlling Ae.aegypti mosquito.

Chemical composition and larvicidal activity of leaf essential oil from Clausena anisata (Willd.) Hook.f.ex Benth (Rutaceae) against three mosquito species

Objective:To determine the mosquito larvicidal activity of leaf essential oil and their chemical constituents from Clausena anisata（C.anisata）（Willd.） Hook.f.ex Benth.against Culex quinquefasciatus,Aedes aegypti and Anopheles Stephensi.Methods:Essential oil was obtained by hydro-distillation and the chemical composition of the leaf essential oil was analyzed using gas chromatography—mass spectrometry.The mosquitoes were reared in the vector control laboratory and twenty lateⅢinstar larvae of three mosquito species were exposed to based on the wide range and narrow range tests,essential oil was tested at 50.100.150,200 and 250 ppm and each compound was tested at various concentration（5-75 ppm） and were assayed in the laboratory by using the protocol of WHO 2005:the 24 h LC50 values of the C.anisata leaf essential oil and their major compounds were determined following Probit analysis.Results:The oil contained were mainlyβ-pinene（32.8%）,sabinene（28.3%）,germacrene-D（12.7%）,estragole （6.4%） and linalool（5.9%）.The essential oil from the leaves of C.anisata exhibited significant larvicidal activity,with 24 h LC50 values of 140.96,130.19 and 119.59 ppm.respectively.The five pure constituents extracted from the C.anisata leaf essential oil were also tested individually against three mosquito larvae.The LC50 values ofβ-pinene,sabinene,germacrene-D,estragole and linalool appeared to be most effective against Anopheles stephensi(LC50-23.17,19.67,16.95. 11.01,35.17 ppm) followed by Aedes aegypti(LC50-27.69,21.20,18.76,12.70,38.64 ppm) and Culex quinquefasciatus(LC50-32.23,25.01.21.28,14.01,42.28).Conclusions:The essential oil of C. anisata contains five major compounds and has remarkable larvicidal properties,which may be considered as a potent source for the production of natural larvicides.

Larvicidal and repellent activities of Sida acuta Burm.F.(Family:Malvaceae) against three important vector mosquitoes

Objective:To determine the larvicidal and repellent activities of Sida acuta Burm.F.（Family: Malvaceae）extract against Culex quinquefasciatus,Aedes aegypti and Anopheles stephensi. Methods:Twenty five late III instar larve of three mosquito species were exposed to various concentrations（15-90 mg/L） and were assayed in the laboratory by using the protocol of WHO 2005:the 24 h LC50 values of the Sida acuta leaf extract was determined following Probit analysis. The repellent efficacy was determined against three mosquito species at three concentrations viz.,1.0,2.5 and 5.0 mg/cm2 under the laboratory conditions.Results:Results showed varying degree of larvicidal activity of crude extract of Sida acuta against three important mosquitoes with LC50 values ranging between 38 to 48 mg/L.The crude extract had strong repellent action against three species of mosquitoes as it provided 100%protection against Anopheles stephensi for 180 min followed by Aedes aegypti（150 min） and Culex quinquefasciatus（120 min）.Conclusions: From the results it can be concluded the crude extract of Sida acuta was an excellent potential for controlling Culex quinquefasciatus,Aedes aegypti and Anopleles stephensi mosquitoes.

Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease:A systematic review

This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease(IBD).Specifically,the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers.Relevant articles published up to December 2022 were identified through a search of the PubMed,Scopus,Web of Science,and Embase databases.The search used keywords including“inflammatory bowel disease”,“medicinal plants”,“natural molecules”,“anti-inflammatory”,and“ulcerative colitis”,and identified 1,878 potentially relevant articles,of which 89 were included in this review after completion of the selection process.This study provides preclinical data on natural products(NPs)that can potentially treat IBD,including ulcerative colitis.The main actions of these NPs relate to their effects on nuclear factor kappa B(NF-κβ),the Janus kinase(JAK)/signal transducer and activator of transcription(STAT)signaling pathway,the regulation of T helper 17/regulatory T cells balance,and oxidative stress.The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,and IL-17,via the Jun N-terminal kinase(JNK)1,NF-κβ-p65,and STAT3 pathways.In addition,NPs were shown to reduce oxidative stress and the severity of ulcerative colitis,as well as increase the activity of antioxidant enzymes.These actions suggest that NPs represent a promising treatment for IBD,and potentially have greater efficacy and safety than current treatments.

A Comprehensive Review on Preclinical Safety and Toxicity of Medicinal Plants

Background:Globally,80%people use plant-derived products for treating or preventing diseases.One prevalent perception about medicinal plants is that they are safe and devoid of adverse effects.However,approximately 1,50,000 plants contain toxic substances.Objective:The present review focuses on medicinal plant extracts/fractions toxicity assessments made in preclin-ical models by oral route.Methods:Detail studies were searched from databases including PubMed and Google Scholar.A manual reference screening of the selected studies was done to identify relevant articles,with no language restriction being imposed at the time of searching.Results:The studies included were performed in rodents,and the test substances were administered orally.Our search revealed 33 widely used plants or products with significant toxicity,and phytochemicals from these plants have been summarized.Through a systematic review,we identified a plethora of medicinal plant extracts reporting safety and toxicity concerns.Conclusion:In the future,preclinical toxicokinetic studies of herbs and the determination of their no-observed-adverse-effect levels are required for a complete safety assessment.Finally,the interaction of herbs with com-monly used/over-the-counter drugs in terms of the latter’s metabolic profile should be undertaken.

Antidepressant-like effects of the ethanolic extract of XiaobuxinTang,a traditional Chinese herbal prescription in animal models of depression

Background Xiaobuxin-Tang, a traditional Chinese herbal prescription recorded in a silk scroll unearthed from Mogao Caves of Dunhuang has been indicated that it can remit depressive disorder. The present study was designed to investigate its antidepressant effects in various animal depression models.Methods Xiaobuxin-Tang was extracted by 70% alcohol, and then three behavioral despair models and 5-Hydroxytryptophan （HTP）-induced head twitch response model were adopted to assess the antidepressant effects of the ethanolic extract of Xiaobuxin-Tang with the study on spontaneous motor activity. Groups of mice and rats received oral treatment with Xiaobuxin-Tang （150-1200 mg/kg） only once acutely in all tests. The duration of immobility was measured during the last 4 minutes of the 6-minutes test period in mice forced swimming test, rats forced swimming test and mice tail suspension test. In 5-HTP-induced head twitch response, the mice were intraperitoneally administered with 120 mg/kg of L-5-HTP, and then the cumulative number of head twitches was counted in 20 minutes. Spontaneous motor activities of mice were recorded automatically in 10 minutes by VIDEOMEX-V image analytic system.Results The extract at doses of 300 mg/kg （p.o.） and 600 mg/kg （p.o.） significantly decreased the duration of immobility time in a dose dependent manner in mice forced swimming test; also, the extract at dose of 1200 mg/kg （p.o.） significantly decreased the duration of immobility time in rat forced swimming test. Furthermore, the extract at a dose of 600 mg/kg had the same effect in mice tail suspension test. Meanwhile, the extract at the effective doses for behavioral despair models, had no effect on spontaneous motor activity in mice. The extract （300-1200 mg/kg, p.o.） also increased the accumulative number of the 5-HTP-induced head twitch response in mice in 20 minutes.Conclusion Our results suggested that the ethanolic extract of Xiaobuxin-Tang exerts antidepressant-like effect.

Chemical composition and laboratory investigation of Melissa officinalis essential oil against human malarial vector mosquito,Anopheles stephensi L.(Diptera:Culicidae)

Objective:To decide the larvicides,ovicidal,pupicidal and repellent activity of Melissa officinalis(M.officinalis)chemical compositions against important mosquito Anopheles stephensi(An.stephensi)(Diptera:Culicidae).Methods:A chemical constituent of 24 compounds was identified in the oils of M.officinalis compounds representing to 98.73%.A total of 253rd instar larvae of An.stephensi were showed to a variety of concentrations(30-300 mg/L)in laboratory by means of utilizing the standard procedure portrayed by World Health Organization(2005).The larvae were exposed for 24 h and mortalities were subjected to probit analysis.The ovicidal activity was strong-minded against An.stephensi mosquito to a variety of concentrations ranging from 15-90 mg/L under the laboratory circumstances.The repellent activity of M.officinalis chemical compositions tested at concentrations of 0.75 and 1.50 mg/cm^(2)was evaluated in a net cage(45 cm×45 cm×40 cm)including 100 blood starving female mosquitoes of An.stephensi using the methods of World Health Organization(1996).Results:The LC_(50)and LC_(90)values of citronellal compound against An.stephensi larvae were 85.44 and 159.73 mg/L,respectively.Mean percent hatchability of the ovicidal action was observed 48 h post-treatment.Similarly,the citronellal compound and other compositions were found to be mainly effective against eggs of An.stephensi.Citronellal compound exerted 45,60,75 and 90 mg/L against An.stephensi,respectively.The repellent activity of citronellal compound was contained to be mainly effective and the maximum action was observed at 0.75 and 1.50 mg/cm^(2)concentrations giving 100%protection up to 210 min against An.stephensi.Conclusions:This current study was undertaken to evaluate the larvicidal,ovicidal,repellent potential of compounds from the M.officinalis essential oil against An.stephensi.This is initial statement on the mosquito larvicidal,ovicidal and repellent activity of M.officinalis chemical compositions.