Acute Oral Toxicity Study Research Articles

Acute oral toxicity study of polyherbal formulation: Constac granules

Abstract BACKGROUND: Constipation is a common and frequently persistent gastrointestinal motility condition. It affects the economic burden, the standard of living, social interaction, and the capacity to carry out everyday tasks. This study aimed to evaluate the acute oral toxicity of Constac granules in Wistar rats. METHODS: A total of 12 rats were randomly divided into four groups of three each. Group 1 served as the control and received only distilled water, while groups 2 and 3 received doses of 2000 mg/kg body weight of Constac granules, and group 4 received doses of 5000 mg/kg body weight of Constac granules. The rats were observed for 14 days for any signs of toxicity. Necropsy was performed on all rats at the termination of the study and gross pathology was recorded. RESULTS: The results showed no clinical signs of toxicity or mortality observed in any of the control and treatment groups rats during the 14-day observation period. The LD50 value was estimated to be greater than 5000 mg/kg body weight. CONCLUSION: The acute oral toxicity study of Constac granules in Wistar rats showed no toxicity at doses up to 5000 mg/kg body weight. These findings showed that the oral administration of the Constac granules is safe to use.

An experimental evaluation of anticonvulsant activity of aqueous extract of Caralluma dalzielii N.E. Brown

Ethnopharmacological RelevanceCaralluma dalzielii belongs to the family of Asclepiadiaceae. It is a succulent perennial plant widely distributed across the Sahel region from Senegal to Northwest Nigeria. Extracts from Caralluma dalzielii are used traditionally in the treatment of pain, infertility, epilepsy and other neurological diseases. Aim of the studyThe aim of the present study was to evaluate the anticonvulsant effects of aqueous extracts of aerial parts of Caralluma dalzielii using various experimental models. Materials and methodsThe anticonvulsant effect of the plant extract (250, 500 and 1000 mg/kg p.o) were assessed using maximal electroshock (MES) model in chicks, pentylenetetrazole (PTZ) and strychnine (STN)-induced seizures models in mice. Diazepam-induced sleep in chicks was used to study the sedative property of the plant. In the anticonvulsant and sedative property studies, the onset and duration of seizures and sleep were recorded respectively. The oral acute toxicity study was assessed. The extract was screened preliminarily for its phytochemicals and was further analysed using Gas chromatography-mass spectrometry (GC–MS) to identify its major chemical components. ResultsThe oral acute toxicity studies showed that the LD50 was greater than 5000 mg/kg in mice. Pre-treatment of mice with the aqueous extract of Caralluma dalzielii produced a dose-dependent protection against PTZ-induced seizures and mortality with 100% protection at the highest dose of the extract. The extract also significantly increased the latency/onset of myoclonic jerks and reduced the duration of tonic seizures dose dependently. In STN-induced seizure, the extract had no protection against seizure induction similar to diazepam the positive control. However, it significantly (p < 0.05) prolonged the latency of seizure and increased the survival time before death in a dose dependent manner. Caralluma dalzielii had zero protection against maximal electroshock. Phytochemical screening showed the presence of flavonoids, tannins, saponins, steroids, glycosides, cardiac glycosides and phenols. GC–MS analysis revealed the presence of some compounds. ConclusionThe extract of Caralluma dalzielii possesses anticonvulsant activity with less marked sedative activity. It also contains several phytochemicals which may be responsible for the activity. This study serves to validate the use of this plant in folkloric medicine for the treatment of epilepsy and convulsions.

Oral acute and subchronic (28-day) toxicity studies of snakehead fish (Channa striata)

Food and drug control authorities in each country have issued warnings about the toxic effect potential of using commonly consumed traditional medicines. The safety assurance, standardization, and market regulation of herbal medicines being sold need to be determined. This study's goal is to investigate the acute and subchronic toxicity of cold-processed snakehead fish (Channa striata) flesh. In-vivo rats models were given dosages of 350, 1400, and 5600 mg/kg processed snakehead fish (SF) and were monitored for toxic symptoms and mortality for 14 days. Meanwhile, regarding subchronic toxicity, doses of 350, 700, and 1400 mg/kg SF were administered orally for 28 days. Afterward, the animal subjects were sacrificed for histopathological, hematological, and biochemical examinations. There were no evidence of toxicity or mortality in rats during the acute examination, which lasted 14 days. The subchronic toxicity results showed no significant changes in most of the hematological, biochemical, and histological profiles of the organs. Some changes observed in blood biochemistry and relative organ weight were assumed as a temporary effect and not a sign of toxicity. The overall results showed that the SF was non-toxic up to 1400 mg/kg, which can be considered a safe dose for the application of health supplement raw materials.

Assessment of toxicity and genotoxic safety profile of novel fisetin ruthenium-p-cymene complex in mice.

Throughout the last decades flavonoids have been considered as a powerful bioactive molecule. Complexation of these flavonoids with metal ions demonstrated the genesis of unique organometallic complexes which provide improved pharmacological and therapeutic activities. In this research, the fisetin ruthenium-p-cymene complex was synthesized and characterized via different analytical methods like UV-visible spectroscopy, Fourier-transform infrared spectroscopy, mass spectroscopy, and scanning electron microscope. The toxicological profile of the complex was evaluated by acute and sub-acute toxicity. Additionally, the mutagenic and genotoxic activity of the complex was assessed by Ames test, chromosomal aberration test, and micronucleus based assay in Swiss albino mice. The acute oral toxicity study exhibited the LD50 of the complex at 500mg/kg and subsequently, the sub-acute doses were selected. In sub-acute toxicity study, the hematology and serum biochemistry of the 400mg/kg group showed upregulated white blood cells, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, glucose and cholesterol. However, there was no treatment related alteration of hematological and serum biochemical parameters in the 50, 100, and 200mg/kg group. In the histopathological analysis, the 50, 100, and 200mg/kg groups were not associated with any toxicological alterations, whereas the 400mg/kg group showed prominent toxicological incidences. Nevertheless, the treatment with fisetin ruthenium-p-cymene complex did not exhibit any mutagenic and genotoxic effect in Swiss albino mice. Thus, the safe dose of this novel organometallic complex was determined as 50, 100, and 200mg/kg without any toxicological and genotoxic potential.

Synthesis, characterization, and acute toxicity of pH-responsive Salvia spinosa mucilage-co-acrylic acid hydrogel: A smart excipient for drug release applications

Owing to the increasing demand for pH-responsive excipients based on natural polysaccharides, a copolymeric biocomposite material was developed for sustained release drug delivery system (DDS). A novel pH-responsive, non-toxic, and superabsorbent graft copolymeric hydrogel (SSH-co-AA) based on mucilage from Salvia spinosa seeds (SSH) and acrylic acid (AA; monomer) was fabricated through free radical copolymerization using N,N′-methylene-bis-acrylamide (MBA; cross-linker) and potassium persulfate (KPS; initiator). The Fourier transform infrared and CP/MAS 13C‐NMR solid-state NMR spectroscopic analyses confirmed the successful grafting of AA onto SSH. The Powder X-ray diffraction analysis indicated the complete entrapment of crystalline drug in the amorphous polymeric network. Newly fabricated hydrogel is thermally more stable than SSH as revealed through thermogravimetric analysis (TGA). The scanning electron microscopic images indicated the porous nature of SSH-co-AA. An increase in the gel fraction is observed by increasing the concentration of SSH, AA, and MBA. The porosity of SSH-co-AA is directly proportional to the concentration of SSH and AA and inversely proportional to the concentration of MBA. The swelling of SSH-co-AA followed second-order kinetics and the sustained release of venlafaxine HCl followed the Korsmeyer-Peppas model and non-fickian diffusion mechanism. Acute oral toxicity studies of SSH-co-AA reported non-toxic and non-irritant attributes.

Evaluation of the acute oral toxicity and antipsychotic activity of a dual inhibitor of PDE1B and PDE10A in rat model of schizophrenia.

Phosphodiesterase 1B (PDE1B) and PDE10A are dual-specificity PDEs that hydrolyse both cyclic adenosine monophosphate and cyclic guanosine monophosphate, and are highly expressed in the striatum. Several reports have suggested that PDE10A inhibitors may present a promising approach for the treatment of positive symptoms of schizophrenia, whereas PDE1B inhibitors may present a novel mechanism to modulate cognitive deficits. Previously, we have reported a novel dual inhibitor of PDE1B and PDE10A, compound 2 [(3-fluorophenyl)(2-methyl-2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)methanone] which has shown inhibitory activity for human recombinant PDE1B and PDE10A in vitro. In the present study, the safety profile of compound 2 has been evaluated in rats in the acute oral toxicity study, as well as; the antipsychotic-like effects in the rat model of schizophrenia. Compound 2 was tolerated up to 1 g/kg when administered at a single oral dose. Additionally, compound 2 has strongly suppressed ketamine-induced hyperlocomotion, which presented a model for the positive symptoms of schizophrenia. It has also shown an ability to attenuate social isolation induced by chronic administration of ketamine and enhanced recognition memory of rats ​in the novel object recognition test. Altogether, our results suggest that compound 2 represents a promising therapy for the treatment of the three symptomatic domains of schizophrenia.

Hemotoxicity of Hairy Fig (Ficus hispida L.f.) Fruits on Male Wistar Rats (Rattus norvegicus Berkenhout, 1769)

Hairy fig (Ficus hispida) fruits (HFF) are widely consumed as food and traditional medicine in several West Asian countries, both the unripe fruit (UHFF) and ripe fruit (RHFF). However, they are not commonly utilized in Indonesia. Acute oral toxicity studies reported No Observed adverse effect level (NOAEL). Further, a reproductive toxicity study found that UHFF boosted spermatogenesis and increased the quality and quantity of spermatozoa. Meanwhile, RHFF exhibited the opposite effects. To provide comprehensive information from the previous study, this research was conducted to evaluate the hemotoxicity of UHFF and RHFF about their impact on the male reproductive system. Nine Wistar rats were assigned into three groups: the first group received UHFF juice, the second group received RHFF juice, and the third group received distilled water as control. The volume of each treatment was 2 mL/individual/day for 77 days. On days 0, 28, and 77, blood samples were collected for routine hematological profile examination using a hematology analyzer (Sysmex®XP-100). Data were analyzed using a one-way ANOVA test and Duncan's test (α=0.05) to discover significant differences between groups and times. Results showed that consuming hairy fig fruit, especially the UHFF, had an unfavorable effect on erythrocytes resulting in hypochromic microcytic anemia. Still, there was no adverse effect on leukocytes and platelets. Anemia may have occurred due to the presence of hemotoxic compounds that interfere with the synthesis and binding of hemoglobin or because the hairy fig fruit filtrates were oxidized, thereby increasing the level of oxidative stress within the body, of which is a drop in hemoglobin levels.

EVALUATION OF ANTIASTHMATIC ACTIVITY OF SEED EXTRACTS OF APIUM GRAVEOLENS LINN

anti-asthmatic potential is one of them In view of this, the present study was undertaken to investigate the anti-asthmatic potential of the seeds of Apium graveolens Linn. In this study first, extract was prepared using Soxhlet apparatus with continuous heat extraction method in 95% v/v ethanol. The total yield obtained from extraction was found to be 34% w/w. Then Preliminary Phytochemicals Screening was carried out for by using different types of chemical tests. The result of phytochemical screening shows that ethanolic extract contained flavonoids, steroids and terpenoids. Then Acute Oral Toxicity study for determination of LD50 was done by Dose Fixation method according to OECD guideline (AOT 425). This was performed in Swiss Albino mice. The observation of this study confirmed that, LD50 of the compound was to be greater than 2000mg/kg for the test compound. Any dose below 2000mg/kg could be used as a dose for animals and evaluation of anti-asthmatic activity was carried out at doses of 50, 100 and 200 mg/kg body weight by using milk induced leukocytosis and eosinophilia. Total Leukocyte Count and Differential Leukocyte Count were done by Haemocytometry and Field Staining Method respectively. Statistical analysis carried out by Student t-test, one way ANOVA and followed by Dunnett’s test using PRISM Software (Graph Pad PRISM Version 5.03). The ethanolic extract showed significant inhibition against leukocytosis and eosinophilia induced by milk as compared to disease control, among three doses the 100mg dose showed significant * (P &lt; 0.05) effect of EEAG on milk induced Leucocytosis and eosinophilia. Group of mice which were pre-treated with EEAG (200 mg/kg p.o.) demonstrate significant *** (P &lt; 0.05) effect of EEAG on milk induced Eosinophilia.

PH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies.

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45-83.54% and 50.13-72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

Cytotoxicity, oral toxicity, genotoxicity, and mutagenicity evaluation of essential oil from Psidium glaziovianum Kiaersk leaves

Ethnopharmacological relevanceMembers of the Psidium genus have been suggested in ethnobotanical research for the treatment of various human diseases, and some studies have already proven their popular uses through research, such as Psidium glaziovianum, which is found in Brazil's northeast and southeast regions and has antinociceptive and anti-inflammatory properties; however, the safety of use has not yet been evaluated. Aim of the studyThis study investigated the safety of using essential oil obtained from P. glaziovianum leaves (PgEO) in vitro and in vivo models. Materials and methodsCytotoxicity was evaluated in murine erythrocytes, while acute toxicity, genotoxicity (comet assay) and mutagenicity (micronucleus test) studies were performed using Swiss albino mice. ResultsIn the cytotoxicity assay, the hemolysis rate indicated a low capacity of PgEO to cause cell lysis (0.33–1.78%). In the acute oral toxicity study, animals treated with up to up to 5000 mg/kg body weight did not observe mortality or physiological changes. Neither dosage caused behavioral problems or death in mice over 14 days. The control and 2,000 mg/kg groups had higher feed intake and body weight than the 5,000 mg/kg PgEO group. Erythrocyte count, hemoglobin level, mean corpuscular volume, and MCV decreased, but serum alanine and aspartate aminotransferases increased. In the genotoxic evaluation, 5000 mg/kg PgEO enhanced nucleated blood cell DI and DF. ConclusionsThe present study describes that PgEO can be considered well tolerated in acute exposure at doses up to 2000 mg/kg, however the dose of 5000 mg/kg of PgEO should be used with caution.

A toxicological evaluation for safety assessment of ruthenium-based diosmetin complex in rats

The flavonoid-based organometallic complexes have been identified as novel bioactive compounds with enhanced pharmacological and therapeutic activity. In this study, the ruthenium-p-cymene diosmetin complex was synthesized, characterized, and investigated for toxicological profiling through different toxicological and genotoxicological studies which include acute and sub-acute toxicity, chromosomal aberration, and bone marrow micronucleus study. The acute oral toxicity study demonstrated the LD50 dose of the complex at 500 mg/kg body weight which further instigated the sub-acute doses i.e. 50, 100, and 200 mg/kg. The histopathological analysis demonstrated that the 400 mg/kg dose was associated with severe toxicological incidences of the vital organs (liver, kidney, pancreas, testis, and stomach) except the ovary with increased levels of ALP, AST, ALT, and WBC count. However, 50, 100, and 200 mg/kg doses did not show any toxicological alteration and maintained the normal levels of hematological and serum biochemical parameters. The genotoxicological assessment of the complex depicted no such genetic damage or mutagenicity in any complex treated groups. In conclusion, the 50, 100, and 200 mg/kg doses were determined as therapeutic dose of the novel ruthenium-p-cymene diosmetin complex without any genotoxic and mutagenic potential which can be further implemented in the investigation of various pharmacological and therapeutic interventions.

Effects on Lettuce Yield Parameters and Toxicological Safety Assessment of a Plant-Derived Formulation Based on Rosemary and Eucalyptus Essential Oils

Essential oils from medicinal and aromatic plants are increasingly recognized as a promising class of green molecules for use in crop production. In many cases, the beneficial aspects of a substance are not supported by sufficient toxicological safety testing, even though recent reports suggest that some compounds may be toxic to terrestrial or aquatic non-target species. It is, therefore, essential to investigate the possibility of adverse effects on non-target animals and humans exposed to these substances through the consumption of fruit and/or vegetables. The present study aims to examine the potential effects on yield and quality parameters and investigate the level of in vitro and in vivo toxicity of an Eco-product (EP) based on rosemary and eucalyptus essential oils, to provide a measure for safe use in the agricultural sector. The product was evaluated in lettuce crop production and indicated that one-time application of the EP formula increases yield, activating various secondary metabolism pathways of the plant to cope with oxidative stress. Cytotoxicity assays and in vivo acute oral and dermal toxicity studies suggest that the tested compound does not pose any significant health hazard, and the dissolved product can be classified in Category 5, according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

Acute and sub-acute oral toxicity of the methanol extract of Adansonia digitata fruit pulp.

Most rural and urban-based communities in Africa rely on traditional remedies for their primary healthcare. One probable reason for this is the assumption that they are free of harmful side effects and toxicity, compared to orthodox drugs. However, very few plants have been thoroughly evaluated for their toxic effects. Adansonia digitata (A. digitata) also known as (Baobab) is a member of the Malvaceae family. Almost all components of the tree are utilized in traditional African medicine. The present study evaluated the potential toxicity of methanol extract from the fruit pulp of Adansonia digitata through acute and sub-acute oral administration in rats. The acute oral toxicity study was done according to Organization of Economic Co-operation and Development (OECD) guidelines no 425 using a limit dose of 2000 mg/kg body weight (BW). Sub-acute oral toxicity using (250, 500, and, 1000 mg/kg BW) was performed by daily administration for 28 days according to the OECD guideline 407. The acute toxicity study revealed no lethal effects and behavioral signs of toxicity at the tested dose indicating that LD is greater than 2000mg/kg. In the sub-acute study, no significant difference was observed in the body weight, organ weight, liver, and kidney parameters in all treated groups compared to the control. A non-significant decrease in packed cell volume (PCV) was observed across the groups. Also, a significant increase in the white blood cell count and a decrease in the lymphocyte count occurred in the group treated with 250 mg/kg BW. These results show that methanol extract of Adansonia digitata fruit pulp is generally safe on short-term use but can cause changes in haematological parameters on long-term use.

Fabrication of pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 for the controlled release of ketorolac: its characterization and acute oral toxicity study

Objective Ketorolac tromethamine (KT), selected as a model drug, is used in management of moderate to severe acute pain. It has a short half-life (∼5.5 h) and requires frequent dose administration when needed for longer period of time. In our current project, we designed pH responsive hydrogel blends of chondroitin sulfate/pluronic F-127 (CS/Pl) for the controlled release of ketorolac. Methods Hydrogel blends were fabricated using free radical polymerization reaction technique utilizing different ratios of chondroitin sulfate (CS) (polymer) and pluronic F-127 (polymer), acrylic acid (monomer), N,N′-methyl-bisacrylamide (MBA) (cross-linker), initiator ammonium persulfate (APS) and tween-80 (surfactant). The fabricated hydrogel blends were studied and evaluated for pH responsiveness, swelling, water absorbency, in vitro drug release, and morphological characteristics such as SEM, XRD, FTIR, and TGA/DSC. Acute toxicity study was performed on rabbits. Results Maximum swelling and water absorbency were shown by CS/Pl blends being significantly greater at 7.4 (basic pH) than in 1.2 (acidic pH). In vitro dissolution demonstrated pH responsive controlled KT release following zero order at higher pH (7.4) medium up to 36 h. FTIR studies confirmed the structures of our blends; SEM results showed porous framework; thermal studies revealed higher stability of hydrogels than the individual polymers; and XRD confirmed the nature of our blends. Toxicity study revealed the nontoxic nature of the hydrogel blends. Conclusion The prepared CS/Pl hydrogels demonstrated stimuli-controlled release with delivery of drug for prolonged period of time and thus can minimize dosing frequency, safe drug delivery, increased patient compliance and easiness.

Behavioral, Analgesic, Anti-Inflammatory and Acute Oral Toxicity Studies on Poly-Herbal Formulation with Anti-Oxidant and Anti-Cancer Effects

a peer-reviewed, open access online international journal which publishes original research papers. The journal welcomes submission from scholars and experts for possible publication from all over the world. The scope of the journal includes: Pharmaceutical research, chemistry and biochemistry of naturally occurring compounds, biological evaluation of crude extracts, ethnomedicine, traditional and complementary medicine, ethnopharmacology, biomedical research, Biotechnology, Evaluation of natural substances of land and sea and of plants, microbes and animals, pharmacognosy, bioavailability, clinical, pharmacological, toxicological studies and pharmacokinetics of phytochemicals, Isolation and characterization of compounds, structure elucidation, synthesis and experimental biosynthesis of natural Product as well as developments of methods in these areas are welcomed in the journal.

Nonclinical safety evaluation of food colorant lac dye via systematic toxicity profiling with assessment of in vivo antigenic potential.

Lac dye is a natural colorant derived mainly from the insect Kerria lacca (Kerr) and has been used in food and beverage as a red-coloring additive. Despite its increasing use for human consumption as an alternative for allergy-associated cochineal, its toxicity profile remained incomplete to sufficiently assess its safety for the intended use. In this study, we evaluated systemic and genetic toxicity by performing acute and subacute oral toxicity studies in Sprague-Dawley (SD) rats using highly purified lac dye (LD) formulated in water and a battery of genotoxicity tests, respectively. To assess antigenic potentials, we carried out an in vivo passive cutaneous anaphylaxis test. A single dose of LD did not cause mortality at 5000mg/kg body weight (BW), setting oral LD50 of >5000mg/kg BW in SD rats. In the 90-day study, transient salivation without accompanying histopathological lesions in the salivary glands in 200 and 500mg/kg BW groups and red-purple pigmentation on the surface of femora and skulls in 500mg/kg groups were observed as nonadverse effects associated with LD, and no adverse effect was detected in all of the parameters examined, establishing a 500mg/kg BW as no-observed-adverse-effect-level (NOAEL). Furthermore, LD was not mutagenic nor clastogenic in the genotoxicity tests. When tested for antigenicity, LD did not induce anaphylactic skin responses as opposed to the positive reaction by ovalbumin, suggesting a lack of antigenicity. Taken together, these findings provide extended toxicity information on LD with direct evidence supporting the lack of antigenicity, providing essential guidance for its safe use in humans.

Anti-arthritic and toxicological evaluation of ethanolic extract of Alternanthera bettzickiana in rats.

In many developing countries, medicinal plants have long been used for therapeutic purposes due to their low cost and toxicity. This study evaluated the safety and anti-arthritic potential of Alternanthera bettzickiana ethanolic extract (ABEE). Acute oral toxicity (OECD 425) was tested in the safety evaluation. A limit test was used to identify the LD50 value. For an acute oral toxicity study a dose of 2000mg/kg of ABEE was given orally to the treatment group, and the control group received distilled water at a rate of 10ml/kg. Biochemical, hematological, and histopathological analyses were performed after 14days. A formaldehyde 2% w/v solution was injected via i.p. to rats of all groups to prepare the arthritic model. Five groups were divided into control (D.H2O), standard (Diclofenac), and three groups receiving the plant extract at dose levels of 125mg/kg, 250mg/kg, and 500mg/kg respectively. Treatment was continued for 10days. Paw diameter and hematological and biochemical variables were quantified. ELISA was performed for the estimation of inflammatory cytokines. In the acute oral toxicity study, no mortality or morbidity were observed, so the LD50 of this plant was greater than 2000mg/kg. ABEE decreased the paw diameter with the restoration of hematological and biochemical changes. SOD and CAT levels were increased while decreasing the MDA, NO, TNF-α, and IL-6 levels in arthritic rats. It is concluded that the use of A. bettzickiana has low toxicity, and it can be used for the treatment of arthritis.

Toxicological assessment of dihydroberberine.

A battery of studies was conducted to examine the toxicological potential of dihydroberberine (DHBBR), a derivative of berberine (BBR). The genotoxicity studies conducted on DHBBR, including the bacterial reverse mutation test, the mouse lymphoma assay, and the in vivo micronucleus test, showed that DHBBR is non-mutagenic and non-clastogenic. An acute oral toxicity study revealed that the LD50 of DHBBR in female Sprague Dawley rats was greater than 2000mg/kg bw. In a 14-day oral dose range finding study, the maximum tolerated dose was the high dose, 120mg/kgbw/day. Based on a 90-day oral toxicity study in male and female Sprague Dawley rats, it was concluded that the NOAEL for DHBBR is 100mg/kgbw/day, the highest dose tested.

New mechanistic insights on Justicia vahlii Roth: UPLC-Q-TOF-MS and GC–MS based metabolomics, in-vivo, in-silico toxicological, antioxidant based anti-inflammatory and enzyme inhibition evaluation

Justicia vahlii Roth. (acanthaceae) is an important medicinal food plant used in pain relief and topical inflammation. The present study aimed to evaluate phytochemical composition, toxicity, anti-inflammatory, antioxidant and enzyme inhibition potential of n-butanol extract of J. vahlii (BEJv). The extract prepared through maceration was found rich in total phenolic contents (TPC) 196.08 ± 6.01 mg of Gallic acid equivalent (mg GAE/g DE) and total flavonoid contents (TFC) 59.08 ± 1.32 mg of Rutin equivalent (mg RE/g DE). The UPLC-Q-TOF-MS analysis of BEJv showed tentative identification of 87 compounds and 19 compounds were detected in GC–MS analysis. The HPLC-PDA quantification showed the presence of 14 polyphenols amongst which kaempferol (3.45 ± 0.21 µg/ mL DE) and ferulic acid (2.31 ± 1.30 µg/ mL DE) were found in highest quantity. The acute oral toxicity study revealed the safety and biocompatibility of the extract up to 3000 mg/kg in mice. There was no effect of BEJv on human normal liver cells (HL 7702) and very low cytotoxic effect on liver cancer cells (HepG2) and breast cancer cells (MCF-7). In anti-inflammatory evaluation, the BEJv treated groups showed significant inhibition (p < 0.001) of late phase carrageenan induced paw edema at 400 mg/kg and increased the levels of oxidative stress markers; catalase, superoxide dismutase (SOD) and glutathione (GSH) while decreased the inflammatory markers; interleukin-1beta (IL-β) and tumor necrosis factor alpha (TNF-α) in paw tissue of mice. BEJv displayed highest results in Ferric reducing antioxidant power (FRAP) assay 97. 21 ± 2.34 mg TE (trolox equivalent)/g DE, and highest activity 3.32 ± 0.31 mmol ACAE (acarbose equivalent)/g D.E against α-glucosidase. Docking study showed good docking score by the tested compounds against the various clinically significant enzymes. Conclusively the current study unveiled J. vahlii as novel non-toxic source with good antioxidant-mediated anti-inflammatory potential which strongly back the traditional use of the species in pain and inflammation.

Acute, chronic, and genotoxic studies on the protopine total alkaloids of the Macleaya cordata (willd.) R. Br. in rodents.

The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.