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BACKGROUND: Successful endodontic therapy in primary teeth relies on effective microbial control. Although conventional irrigants are effective, they pose risks such as cytotoxicity, unpleasant taste, and tissue irritation. Herbal alternatives offer a safer, biocompatible option, especially suitable for children. AIMS: To evaluate and compare the antimicrobial efficacy of a sequential herbal irrigation protocol with a conventional irrigation protocol in the endodontic treatment of primary teeth. MATERIALS AND METHODS: It is a split-mouth, double-blind, and randomized controlled trial that included 15 pediatric patients aged 4-8 years with bilateral primary molars indicated for pulpectomy. Group I received conventional irrigation with 3% sodium hypochlorite, 17% ethylenediaminetetraacetic acid, and 2% chlorhexidine. Group II underwent sequential herbal irrigation using ethanolic extracts of 12.5% Salvadora persica (Miswak), 20% Azadirachta indica (Neem), 2% tea tree oil, and 10% phytic acid. Pre and postirrigation microbial samples were collected and cultured to quantify Enterococcus faecalis and Prevotella intermedia. Statistical analysis used paired t-tests for intragroup comparisons and one-way analysis of variance for intergroup differences, with significance set at P < 0.05. RESULTS: Both groups showed significant microbial reduction (P < 0.0001). Group I had 90.54% and 87.6% reductions in E. faecalis and P. intermedia, respectively, while Group II achieved 92.2% and 90.54%. Herbal irrigation showed significantly greater E. faecalis reduction (P = 0.025), but P. intermedia reduction was not significant (P = 0.384). CONCLUSIONS: The sequential herbal irrigation protocol showed comparable antimicrobial efficacy to conventional agents, with added benefits of safety, biocompatibility, and reduced cytotoxicity, making it a promising natural alternative in pediatric endodontics.

BACKGROUND: Hospitalized children find difficulty in performing regular oral hygiene procedures. In such cases, direct application of herbal oils such as olive oil, Azadirachta indica (AI) (neem), and Curcuma zedoaria (CZ) (white turmeric) as antiplaque agents could be beneficial in maintaining oral hygiene. AIM: The aim of the study was to evaluate the efficacy of normal saline, extra virgin olive oil (EVOO), EVOO with 35% CZ, and EVOO with 30% AI on dental plaque and the count of Streptococcus mutans, Lactobacillus, and Candida albicans in hospitalized children. SETTINGS AND DESIGN: This was a randomized control trial. MATERIALS AND METHODS: 84 hospitalized children of age group 3-14 years were randomly divided by computer-generated random allocation into Group A-EVOO, Group B-EVOO + 35% CZ, Group C-EVOO + 30% AI, and Group D-normal saline with 21 participants in each group and applied with sterile gauze. The plaque score was recorded and analyzed by Loe and Silness plaque index. In addition, plaque sample for microbial analysis was collected from buccal/lingual surfaces, and CFU count was measured at baseline, 24 h, 48 h, and 72 h. RESULTS: The four groups showed a reduction in plaque score and CFU counts from baseline to 72 h with P < 0.05 indicating a statistically significant difference. Group C has shown significant antimicrobial activity against Group A, Group B, and Group D (P = 0.0001) at 72 h. CONCLUSION: EVOO + 35% CZ showed the best treatment outcome in the reduction of microbial count followed by EVOO + 30% AI and EVOO. All the preparations including normal saline have antiplaque properties with the best outcome achieved in EVOO + 35% CZ and EVOO + 30% AI preparations.

AIM: To compare the clinical and radiographically mixture of zinc oxide with Aloe vera, Curcumin and neem as an obturating material for pulpectomy. MATERIALS AND METHODS: The study comprised of age group 4-8 years children requiring endodontic treatment for at least a single primary molar tooth. Sixty primary molar teeth from 43 children were divided equally and randomly into four study groups. The materials used for obturation were zinc oxide powder (ZnO) and Eugenol (ZOE) (group I), ZnO and Aloe vera Gel (group II), ZnO and Curcumin Powder (group III), ZnO and neem extract (group IV). They were evaluated clinically and radiographically at immediate postoperative and then at 1-, 3-, 6-, and 9-month intervals. RESULTS: At the end of 9 months, the Chi-square test revealed 100% success rate for recovery of pain in group I and III, 66.66% in group II and 93.3% in group IV. The success rates for absence of abscess and for periradicular radiolucency in group I, III, and group IV were 100% and 66.6% for group II. The success rate for periapical radiolucency in group I and group III was 100%, in group II 66.6% and in group IV 93.35%. The success rate for all the groups shows 100% success in terms of pathological root resorption. CONCLUSION: Zinc oxide eugenol has proven to be the best obturating material. ZnO with Aloe vera showed a success rate which is significantly lower than the other medicaments. ZnO with Curcumin and ZnO with neem had shown promising clinical and radiographical results. CLINICAL SIGNIFICANCE: ZnO with Curcumin and ZnO with neem can be used as a root canal filling material in primary teeth with further follow-up studies.

OBJECTIVE: To evaluate the clinical efficacy of a hypericum and neem oil dressing, Primary Wound Dressing [ONE] (1PWD) (Kerecis AG, Switzerland), in a patient population with dehiscence of surgical wounds with critical colonisation/infection. Efficacy was defined as resolution of inflammatory/infective symptoms. METHOD: A randomised, controlled, single-blinded, parallel-arms phase III study was conducted comparing the experimental medication to silver-based dressings. All patients were evaluated at enrolment, on days 7, 14, 21 and 28. Improvement of inflammatory/infective symptoms was measured by detecting seven items of the Bates-Jensen Wound Assessment Tool (BWAT). Pain was assessed using the Numeric Rating Scale (NRS). RESULTS: The study enrolled 99 patients. Follow-up was completed in 49 patients in the experimental group and 48 patients in the control group. Overall BWAT evaluation demonstrated similar outcomes between the groups: t=0.23, p-value=0.81, 95% confidence interval (CI): -13.3-10.8. Furthermore, when evaluating the seven items of the BWAT relating to inflammatory signs, there was not a significant difference between the groups: t=0.38, p=0.35, 95% CI: -2.8-2.7. However, when an analysis using the NRS pain scale was performed, a statistically significant pain reduction was demonstrated in favour of the experimental group: t=7.8, p<0.0001, 95% CI: 2.918-4.8819. CONCLUSION: This randomised controlled trial confirmed the efficacy of 1PWD, an investigational product, in the management of surgical dehiscence with critical colonisation or infection, with the added benefit of significant pain reduction when compared with a silver-based dressing.

Neem (Azadirachta indica) exhibits multiple therapeutic benefits in preclinical studies, but clinical studies are lacking. This clinical study investigated the efficacy and safety of an aqueous A. indica leaf and twig extract (NEEM) on metabolic parameters in subjects with metabolic syndrome (MetS). Subjects were randomized to receive (1) placebo or (2) 125 mg, (3) 250 mg, or (4) 500 mg of NEEM twice daily (n = 20/group) for 12 weeks. Fasting blood sugar (FBS) and insulin, postprandial blood sugar (PPBS), insulin resistance (IR), hemoglobin A1c (HbA1c), endothelial function, circulating markers of inflammation and oxidative stress, lipid profiles, and platelet aggregation were measured at weeks 0, 4, 8, and 12. NEEM supplementation dose dependently improved the trajectories for FBS, PPBS, IR, and HbA1c over time, as well as endothelial function and most markers of inflammation and oxidative stress. Therefore, NEEM may be considered a promising therapeutic to attenuate the hyperglycemia and associated cardiometabolic derangements in people with MetS. Clinical trial registration no.: CTRI/2019/03/018034 [registered on: March 12, 2019].

10. Altern Ther Health Med. 2021 Oct;27(S1):196-203. Neem (Azadirachta Indica A. Juss) Capsules for Prophylaxis of COVID-19 Infection: A Pilot, Double-Blind, Randomized Controlled Trial. Nesari TM, Bhardwaj A, ShriKrishna R, Ruknuddin G, Ghildiyal S, Das A, Pandey AK, Chaudhary N, Soman G, Barde M. CONTEXT: SARS-CoV-2 is a global public-health concern. Interventions to prevent infection are urgently needed. The anti-inflammatory and antiviral effects of neem make it a potential agent for COVID-19 prophylaxis. OBJECTIVE: The study intended to evaluate the prophylactic effects of neem capsules for persons at high risk of COVID-19 infection due to contact with COVID-19 positive patients. DESIGN: The research team designed a prospective, randomized, double-blind, placebo-controlled, parallel-design study. SETTING: The study was conducted at a single center in India. PARTICIPANTS: Participants were 190 healthcare workers at the hospital or relatives of patients with COVID-19 infection. INTERVENTION: Of the 190 participants, 95 were in the intervention group and 95 in the control group. Participants received 50 mg of a proprietary, patent-pending, neem-leaf extract or a placebo orally in capsules, twice a day for 28 days. OUTCOME MEASURES: The number of individuals positive for COVID-19 between baseline and follow-up on day 56 was the primary outcome measure. Secondary measures included an evaluation of neem's safety and its effects on quality of life (QOL) and changes in biomarkers. RESULTS: The mean age of participants was 36.97 years, and 68.42% were male. Total 13 subjects tested positive during the study. All were asymptomatic. Of the 154 participants who completed the study per-protocol, 11 tested positive, 3 in the intervention group and 8 in the control group. The probability of COVID-19 infection in participants receiving the intervention was 0.45 times that of participants receiving the placebo, a relative risk of 0.45, with the effectiveness of the intervention being around 55%. Treatment-emergent adverse events (TEAEs) in both groups were minimal and were of grade 1 or 2 in severity. Biomarkers and QOL remained stable in both groups. CONCLUSIONS: The st

AIM: To assess the effect of Neem versus 2.5% NaOCl as root canal irrigants on the intensity of post-operative pain and amount of endotoxins following root canal treatment of mandibular molars with necrotic pulps. METHODOLOGY: This parallel, prospective, double-blinded, randomized controlled trial with allocation ratio 1:1 was conducted in the out-patient clinic of the Endodontic Department, Faculty of Dentistry, Cairo University, Egypt. Fifty healthy patients with mandibular molars with necrotic pulps were randomly assigned into two equal groups using computer software. In the intervention group, root canals were irrigated using Neem; whilst 2.5% NaOCl was used in the control group. A standard root canal treatment was performed in two visits using ProTaper Next rotary files, with no intracanal medication. Pain intensity was assessed using a numerical rating scale (NRS) 6, 12, 24 and 48 h following instrumentation and canal filling. Endotoxin samples were collected using three paper points before and after canal instrumentation and a sandwich ELISA method was used to quantify the level of endotoxins. Demographic, baseline, and outcome data were collected and analysed using chi-square tests (for the comparisons of categorical variables), Mann-Whitney tests (for non-normally distributed variables) and Student's t tests (for normally distributed variables), A P-value < 0.05 was considered to be statistically significant. RESULTS: The mean pain scores within the two groups decreased continually over time. The mean pain scores in the Neem group were lower than those in the 2.5% NaOCl group at 6, 12, 24 and 48 h following instrumentation and canal filling with no significant difference between them except at 24 h following instrumentation (P = 0.012). Both irrigants significantly reduced endotoxin levels compared to the pre-instrumentation samples (P < 0.001) by 8% for the NaOCL group and 18% for the Neem group. CONCLUSION: Neem and 2.5% NaOCl were not significantly different in terms of reducing the intensity of post-operative pain during all follow-up periods except at 24 h following instrumentation where Neem was associated with lower pain intensity. Both irrigants

OBJECTIVES: This clinical investigation examined the effects of brushing with a test toothpaste containing natural ingredients, that is, clove (Syzgium Aromaticum), aloe vera (Aloe Barbadensis), amla (Emblica Officinalis), neem (Azadirachta Indica), tulsi (Ocimum Basillicum) and honey (from Apis Mellifera) along with zinc salts and fluoride in comparison with a dentifrice formulated with fluoride alone on dental plaque and gingivitis over a 6-month period. MATERIALS AND METHOD: One hundred and eighty (180) subjects with mean plaque index scores greater than 1.5 (Turesky Modified Quigley Hein Plaque Index) and gingival index scores >1.0 (Loe and Silness gingival index) in good general health and who met other study criteria were enrolled in the clinical study. Subjects were evaluated for plaque and gingival index scores and were randomly assigned to perform twice-daily oral hygiene with either the test or the control toothpaste for the next 6 months. One hundred and fifty (150) subjects [test toothpaste (n = 72) and control toothpaste (n = 78)] completed the 6-month clinical study with evaluable data. Post-treatment assessments identical to baseline were conducted after 3-month and 6-month use of an assigned product after subjects refrained from oral hygiene for 12 h prior to each evaluation. Comparisons of the treatment groups with respect to baseline-adjusted gingival, plaque, and bleeding index scores at the follow-up examinations were performed using analyses of covariance (ANCOVA). All statistical tests of hypotheses were two-sided and employed a level of significance of p < 0.05. RESULTS: No significant intergroup differences were noted between treatment groups for age and gender by two-sample t-test and chi-square analyses, respectively (p > 0.05). Furthermore, the treatment groups demonstrated no differences at baseline for plaque, gingival and bleeding index scores by a two-sample t-test (p > 0.05). At 3-month and 6-month examination, the test toothpaste exhibited progressive reductions in plaque, gingival and bleeding scores as compared to control toothpaste as showed by ANCOVA (p < 0.001). In comparison with the control, the test demonstrated reduction

The objective of the present study was to analyze and identify the phytochemical components found in neem leaf extracts using gas chromatography-mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FTIR) methods. The extract samples were acquired using ethyl acetate (EA) and petroleum ether (PE) solvents. Moreover, the extracts were assessed for their antibacterial and antioxidant features. In addition, chitosan nanoparticles (Cs NPs) containing neem extracts were synthesized and evaluated for their potential antibacterial properties, explicitly targeting multi-drug resistant (MDR) bacteria. The neem extracts were analyzed using GC-MS, which identified components such as hydrocarbons, phenolic compounds, terpenoids, alkaloids, and glycosides. Results revealed that the PE extract showed significant antibacterial activity against a range of bacteria. In addition, the PE extract exhibited significant antioxidant activity, exceeding both the EA extract and vitamin C. In addition, both extracts exhibited notable antibiofilm activity, significantly inhibiting the production of biofilm. The Cs NPs, loaded with neem extracts, exhibited significant antibacterial action against multidrug-resistant (MDR) microorganisms. The Cs NPs/EA materials had the greatest zone of inhibition values of 24 ± 2.95 mm against Pseudomonas aeruginosa. Similarly, the Cs NPs/PE materials exhibited a zone of inhibition measurement of 22 ± 3.14 mm against P. aeruginosa. This work highlights the various biochemical components of neem extracts, their strong abilities to combat bacteria and oxidative stress, and the possibility of Cs NPs containing neem extracts as effective treatments for antibiotic-resistant bacterial strains.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive and chemo-resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC. OBJECTIVE: This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells. METHODS: We examined the effects of EAD and paclitaxel alone and in combination in MDA-MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti-migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF-κB translocation. RESULTS: The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC50 concentrations, showed a synergistic effect in MDA-MB-231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel. CONCLUSION: To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen. © 2024 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.

Despite the success of antibiotic discovery, infectious diseases remain the second leading source of death worldwide, while the resistance to antibiotics is among the significant problems in the twenty-first century. Medicinal plants are very rich in phytochemicals which can be structurally optimized and processed into new drugs. Nigeria enjoys a diverse collection of medicinal plants, and joint research has ascertained the efficacy of these plants. Plants such as guava (Psidium guajava), ginger (Zingiber officinale), neem (Azadirachta indica), and moringa (Moringa oleifera) have been found to exhibit broad range of antimicrobial activities. Studies on Nigerian plants have shown that they contain alkaloids, polyphenols, terpenes, glycosides, and others with possible therapeutic potentials. The antimicrobial activities of some new compounds such as alloeudesmenol, hanocokinoside, orosunol, and 8-demethylorosunol, identified from medicinal plants in Nigeria, are not yet explored. Further investigation and optimization of these compounds will facilitate the development of new sets of pharmacologically acceptable antimicrobial agents. This review study revealed the efficacy of medicinal plants as an alternative therapy in combating and curtailing the development and survival of multidrug-resistant pathogens coupled with the toxic effects of some antibiotics. Due to enormous therapeutic possibilities buried in medicinal plants, there is a need for more research into unique fingerprints and novel compounds that can provide cure to the neglected tropical diseases (NTDs) of humans and animals facing Africa, especially Nigeria.

Trehalase catalyzes hydrolysis of trehalose and plays a crucial role in insect metabolism. In the present study, phylogenetic analysis and multiple sequence alignment suggested that H. armigera trehalase-1 (HaTre-1) is closely related to other soluble trehalases with conserved signature features and functional sites. We have expressed and purified recombinant HaTre-1 having Vmax ~0.16mM/min and KM ~1.34mM. Inhibition kinetics and Microscale thermophoresis illustrated competitive inhibition of HaTre-1 by Validamycin A having Ki ~3nM and KD ~542nM, respectively. Docking studies of HaTre-1 with Validamycin A indicated that it binds at the active site with multiple hydrogen bonds. Ingestion of Validamycin A resulted in impediment of H. armigera growth and developmental defects. Treated larvae showed concentration dependent decrease in fecundity. It also led to total inhibition of ex-vivo trehalase activity and down-regulation of gene expression of HaTre-1. Relatively high insect mortality was observed on tomato plants sprayed with combination of Validamycin A with Azadirachta indica (neem) and Pongamia pinnata (karanj) oil as compared to the individual treatments. This report has re-emphasized trehalase inhibition as a potential insecticidal strategy and also recommends Validamycin A as a prospective value-added ingredient to commercial bio-pesticide formulations.

Erratum in Mol Biochem Parasitol. 2017 Jan;211:104. doi: 10.1016/j.molbiopara.2016.07.007. Spironucleus vortens is a protozoan parasite associated with significant mortalities in the freshwater angelfish, Pterophyllum scalare. Control of this parasite is especially problematic due to restrictions on the use of the drug of choice, metronidazole (MTZ), on fish farms. Use of garlic (Allium sativum) is undergoing a renaissance following experimental validations of its antimicrobial efficiency. Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), is a stable transformation product of allicin, the primary biologically active component of garlic. In the current study, an ajoene oil crude extract had a minimum inhibitory concentration (MIC) of 40μg/ml against S. vortens. GC-MS and NMR spectroscopy revealed this ajoene extract contained a mixture of the (E) and (Z)-ajoene isomers along with diallyl disulphide (DADS) and diallyl trisulphide (DATS). The only component of the ajoene crude oil found to substantially inhibit S. vortens growth by optical density monitoring (Bioscreen C Reader) was (Z)-ajoene (MIC 16μg/ml). Ajoene oil acted in synergy with MTZ in vitro, reducing the individual MIC of this drug (4μg/ml) by 16-fold, and that of ajoene oil by 200-fold with a fractional inhibitory concentration (FIC) index of 0.263. This synergistic interaction was confirmed in vivo. S. vortens-infected Pterophyllum scalare angelfish dosed orally with 0.5% (v/w) MTZ combined with 0.05% (v/w) ajoene displayed a significant reduction in faecal trophozoite count, whilst those fed on 0.5% MTZ flakes (half the recommended oral dose) alone did not. This study demonstrates for the first time the synergistic interaction between the synthetic drug MTZ and natural ajoene oil both in vitro and in vivo. Future work should evaluate the potential synergy of ajoene and MTZ against MTZ-resistant bacteria and protists.

The cabbage looper, Trichoplusia ni (Hübner) (Lepidoptera: Noctuidae), is one of the most damaging insect pests of cabbage (Brassica oleracea variety capitata) and broccoli (B. oleracea variety italica) in North America. Leaf-feeding larvae attack crucifer and vegetable crops in greenhouses and fields. Here, we have studied a synthetic feeding deterrent, 1-allyloxy-4-propoxybenzene, and a botanical deterrent, neem (an extract from seeds of Azadirachta indica A. de Jussieu (Meliaceae)), in leaf disc choice bioassays with T. ni. We tested the two deterrents and the combination, and we found that the blend exhibits synergy between the two deterrents. We also tested the deterrents in assays with whole cabbage plants in ventilated enclosures and found that 1-allyloxy-4-propoxybenzene evaporated and, therefore, in that context addition of 1-allyloxy-4-propoxybenzene to neem did not enhance deterrence against T. ni. © 2014 Entomological Society of America.

18. J Environ Biol. 2014 Sep;35(5):917-22. Studies on repellent activity of seed oils alone and in combination on mosquito, Aedes aegypti. Mukesh Y, Savitri P, Kaushik R, Singh NP. The study was undertaken to investigate the relative repellency of Pongamia pinnata and Azadirachta indica seed oils on vector mosquito, Aedes aegypti under laboratory conditions. The repellents were formulated into 3 groups: seed oils, their mixture and combination of seed oils with three carrier oils viz. olive, mustard and coconut oil. Different formulations of each oil were tested at the concentrations of 1% and 5% on human baits. Efficiency was assessed, based on the total protection time; biting rate and percent protection provided by each formulation. Results showed that 5% formulation of the Pongamia pinnata and Azadirachta indica seed oils, mixed in 1:1 ratio exhibited highest percentage repellency of 85%, protection time of 300 min and bite rate of 6%. 5% concentration of A. indica and P. pinnata seed oil in mustard oil base offered 86.36% and 85% protection respectively with total protection time of 230 and 240 min respectively. The study confirms that Azadirachta indica and Pongamia pinnata have mosquito-repellent potential. When mixed in different ratios or with some carrier oil their efficacy increases 2-fold in some cases. These formulations are very promising for topical use (> 5 hrs complete protection) and are comparable to the protection provided by advanced Odomos mosquito repellent cream available commercially and thus are recommended for field trial.

Experiments were conducted at Zonal Agricultural Research Station, Mudigere, India, for two years with an objective to study the population fluctuation, seasonal incidence and evaluation of neem products and insecticides for their efficacy against cardamom shoot fly. During the study period, it was noticed that shoot fly population the increased during the dry months (March, May and October) but was low from June to September months. The population exhibited a negative correlation with rainfall, minimum temperature and maximum relative humidity and positive correlations with maximum temperature and sunshine h. Among the six insecticides tested, phorate, phorate with neem cake and neem cake alone were found superior over other treatments. The present study clearly indicated that application of neem cake helps not only in reduction of shoot fly incidence but also enhances the production of side suckers compared to other treatments.

Cancer chemotherapy is associated with several life threatening complications, including bone marrow suppression and leucopenia. To overcome this problem, colony stimulating factor (CSF), granulocyte colony stimulating factor (GCSF) and granulocyte macrophage colony stimulating factor (GMCSF), can be used, however, these therapeutics are expensive and have several disadvantages, including tumor growth promoting activities. This study attempted to use an immunostimulatory neem (Azadirachta indica) leaf preparation (NLP) to prevent the cyclophosphamide (CYP) induced reduction in the WBC count. Pretreatment of mice with NLP reduced the extent of leucopenia and neutropenia in normal and tumor bearing CYP treated mice. NLP pretreatment enhanced in vitro tumor cell cytotoxicity by peripheral blood mononuclear cells (PBMC) from CYP treated mice in either normal or tumor bearing conditions. Similarly, NLP pretreatment of mice enhanced the CYP mediated in vivo tumor growth inhibition and survivability of the host. Based on these observations, it is concluded that NLP would be an effective tool to reduce CYP-induced hematological complications. Copyright (c) 2006 John Wiley & Sons, Ltd.

The biological activity of 6beta-hydroxygedunin isolated from Azadirachta indica A. Juss. was assessed using the gram pod borer, Helicoverpa armigera (Hubner), and Asian armyworm, Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae), alone and in combination with other limonoids, gedunin, salannin, nimbinene, and azadirachtin. The compound exhibited growth inhibitory activity in artificial diet bioassays, with 24.2 and 21.5 ppm, respectively, inhibiting growth by 50%. This efficacy was higher in comparison to gedunin (EC(50) = 50.8 and 40.4 ppm), salannin (EC(50) = 74.5 and 72.0 ppm), and nimbinene (EC(50) = 391.4 and 404.5 ppm). Azadirachtin, however, remained the most active neem allelochemical against both insect species. Nutritional assays clearly demonstrated that, though relative consumption and growth rates of fourth instar larvae were reduced, gedunin-type compounds induced physiological toxicity, evident by reduced efficiency of conversion of ingested food (ECI) in feeding experiments. Salannin and nimbinene, on the contrary, induced concentration-dependent feeding deterrence only. In feeding experiments, combinations of the compounds revealed that when azadirachtin was present in a mixture, EC(50) values did not deviate from the individual efficacy of azadirachtin (0.26 and 0.21 ppm, respectively) against H. armigera and S. litura larvae. However, a combination without azadirachtin did show a potentiation effect with potent EC(50) values among structurally different molecules, i.e., when salannin or nimbinene was combined with 6beta-hydroxygedunin or gedunin rather than structurally similar salannin + nimbinene or 6beta-hydroxygedunin + gedunin. Obviously, azadirachtin being the most active compound in neem is not synergized or influenced by any other limonoid, but other non-azadirachtin limonoids were more potent in specific combinations vis-à-vis the structural chemistry of the compound. It is obvious from the present study that potentiation among non-azadirachtin limonoids having explicitly two different modes of action, such as feeding deterrence and physiological toxicity, may be playing a significant role in the potentiation effect.

Repellent action of neem oil was evaluated against different mosquito species. 2% neem oil mixed in coconut oil provided 96-100% protection from anophelines, 85% from Aedes, 37.5% from Armigeres whereas it showed wide range of efficacy from 61-94% against Culex spp. Therefore, neem oil can be applied as a personal protection measure against mosquito bites.

23. Southeast Asian J Trop Med Public Health. 1994 Sep;25(3):608-10. Evaluation of neem oil as sandfly, Phlebotomus papatasi (Scopoli) repellent in an Oriental sore endemic area in Rajasthan. Dhiman RC(1), Sharma VP. Author information: (1)Malaria Research Centre (ICMR), Delhi, India. PMID: 7777937 [Indexed for MEDLINE]

PURPOSE: Given the increasing interest in natural and sustainable oral hygiene options, this systematic review evaluates the efficacy of traditional oral hygiene practices, specifically miswak and oil pulling, in maintaining oral health compared with conventional practices, addressing the question: how do these practices affect plaque and gingival outcomes relative to toothbrushing and standard rinses? We hypothesized non-inferiority for short-term plaque/gingivitis control, with limited evidence for longer-term outcomes. MATERIALS AND METHODS: A systematic review was conducted following PRISMA guidelines. Comprehensive literature searches were performed in PubMed, Embase.com, Global Health (CABI), Scopus, and Web of Science up to April 2024 using predefined inclusion criteria, focusing on randomized controlled trials and quasi-experimental designs that evaluated traditional oral hygiene methods against conventional practices. Data extraction, quality assessment, and risk bias analysis were conducted independently by two reviewers. Preliminary pilot searches (targeted scoping) were undertaken to refine concepts, eligibility criteria, and keywords. No formal scoping review was registered. RESULTS: Thirty-one studies met the inclusion criteria. Miswak statistically significantly reduced plaque accumulation and gingival inflammation, performing comparably to or better than conventional toothbrushes. Herbal dentifrices and mouthwashes containing neem, clove, turmeric, and ginger exhibited antimicrobial properties and were as effective as fluoridated products in reducing plaque and gingival inflammation. Oil pulling with sesame or coconut oil showed moderate reductions in microbial load and improved gingival health, though findings varied compared to chlorhexidine mouthwash. Indigenous methods, (e.g., finger brushing, twigs, charcoal) offered accessibility and sustainability benefits but lacked extensive clinical validation. CONCLUSION: Traditional oral hygiene practices may offer benefits similar to conventional methods. Nonetheless, methodological limitations and variability among studies necessitate cautious interpretation of these findings. Further thorough resea

BACKGROUND: Neophytadiene (NPT) [C20H38] or 7, 11, 15-Trimethyl-3-methylenehexadec-1-ene is a diterpene found in the important oil of various plants, including neem (Azadirachta indica). It possesses inhibitory properties against a range of enzymes. The prospective uses of neophytadiene in cosmetics, medicine, and agriculture have attracted much interest. Numerous pharmaceutical applications have been demonstrated, such as analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-malarial, insecticidal, and neuroprotective properties. The extraction, purification, and biological uses of neophytadiene have received special attention. Drugs based on phytocompounds are being developed to create affordable treatments with minimal side effects and a wide range of therapeutic uses. PURPOSE: An overview of the function of neophytadiene is given in this article, along with information on its biological application, pharmacological significance, clinical uses, and its safety concerns. METHODS: A systematic literature review has been conducted using the PRISMA flow technique. Data for the literature survey was gathered online from various journals, computational databases, and search engines like Scopus, PubMed, Science Direct, and Google Scholar until March 2025. RESULTS: The biological efficiency of neophytadiene was affirmed using several in vitro and animal model approaches. The efficacy, therapeutic utility and mechanism of neophytadiene against a range of disorders have all been attempted to be assessed. Neophytadiene plays an important role in the anti-inflammation pathway by TLR4 activation and neuroprotective role by PI3K/Akt signaling pathway. Notably, neophytadiene has shown efficacy against a wide range of organisms, including the malaria parasites. This molecule has multiple uses that can help reduce the severity of certain diseases. It also has the potential to be used as a pharmaceutical ingredient. To maximize its advantages, future research will examine the combined effects of neophytadiene with those of other medications and naturally occurring substances. The acceptance of these phytocompounds as potential medications is clarified by elaborating on the

Recent advancements in nanogel formulations have significantly enhanced the therapeutic efficacy of herbal medicines in wound healing applications. This systematic review explores the integration of various herbal extracts and bioactive compounds into nano gels, highlighting their improved properties and wound healing application. Key formulations include tobacco stem nanogels demonstrating stability and rapid wound contraction, neem and silk fibroin hydrogels accelerating wound regeneration, and curcumin nanosuspension-based nanogels significantly enhancing wound contraction rates. Additional formulations, such as Sansevieria trifasciata hydrogels and emodin-based double network hydrogels, showed substantial reductions in wound size and increased cell proliferation. The incorporation of herbal extracts and bioactive compounds like Bletilla striata, curcumin, calendula, and Hibiscus rosa-sinensis further exhibited enhanced coagulation, antioxidant effects, and fibroblast proliferation. This review highlights the promising future of herbal nanogels in biomedical applications, offering a synergistic approach that combines the benefits of traditional herbal medicine with advanced nanotechnology.

BACKGROUND: A comprehensive summary of evidence about oral health in slum settings that could inform policy directions is lacking. OBJECTIVE: To summarise the latest evidence regarding oral disease burden and their determinants, perceptions, practices, and service utilization in the slums and non-slum urban settings of LMICs. DESIGN: Systematic review. DATA SOURCES: Embase and MEDLINE (Ovid); PubMed; Scopus, Web of Science, CRD DARE Database; ELDIS; Essential Health Links; HINARI; African Index Medicus (AIM); and Bioline International, all searched from January 2000 to June 2023 using slum-related terms. ELIGIBILITY CRITERIA: Empirical studies of all designs were eligible. Studies published in English with full-text available and reporting disease burden, perceptions, behaviours and service utilisation related to oral health of residents of slums or broader settings including slums in low and middle-income countries were included. DATA EXTRACTION, QUALITY ASSESSMENT, SYNTHESIS AND REPORTING: Studies were categorised and data were extracted and charted according to a preliminary conceptual framework refined by emerging findings. The Mixed Methods Assessment Tool (MMAT) was used to appraise the quality of empirical studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and (where applicable) the Synthesis Without Meta-analysis (SWiM) guideline were adopted for guiding synthesis and reporting. Results were tabulated and narratively summarised. RESULTS: Full-text articles for 56 records were assessed for eligibility and 23 of the articles were included in this review. The majority (13 studies, 57%) were conducted in Asia, and nine studies (39%) in Africa. Six focused on slums (two examined slum and urban non-slum and four examined purely slum settings), two examined general urban settings, eight included both rural and urban areas in their settings, two examined disadvantaged/low socioeconomic, one assessed rural/urban/metropolis/municipal/district, three covered the national population or whole country, and one looked at high versus low socioeconomic regions. The commonest oral diseases reported were dental caries (preva

OBJECTIVES: Although skin disorders in children and adolescents are increasingly treated with phytotherapies in practice, there are very few studies investigating this topic, and no systematic review exists that summarizes the current state of research. This review examines which herbal medicines show to be effective to treat atopic dermatitis, diaper dermatitis, and skin lesions or wounds. METHODS: Clinical studies were searched according to PRISMA-guidelines in the medical databases of PubMed, EMBASE, and CINAHL and summarised in a systematic review. RESULTS: Among the 429 articles screened, 17 studies with a total of 2358 participants were identified that suited our inclusion criteria. Thereof seven studies each on the treatment of atopic dermatitis and skin lesions or wounds and three on diaper dermatitis. The phytotherapeutics investigated were based on the following herbs: Evening primrose, blackcurrant, polypodium leucotomos, calendula, aloe vera, chamomile, comfrey, hamamelis, olive, hypericum, neem, white oak, and myrrh. They have mainly been analysed in randomized controlled trials, but also in (long-term) observational studies, prospective trials and case series. CONCLUSIONS: Based on the application of the Jadad score, eight out of 17 of the studies examined were of low quality. Yet we found some indication that evening primrose oil may be effective for treating atopic dermatitis in children, while comfrey appears to have a positive effect on wound healing. Interestingly, none of the studies found positive effects for treating skin disorders with aloe vera or chamomile.

CONTEXT: Sodium hypochlorite, a gold standard for irrigation in endodontics, has disadvantages like toxicity and root dentin weakening. Alternatives derived from natural products are being explored. AIMS: This systematic review was done to understand the clinical benefits of natural irrigants when compared with a standard irrigant, sodium hypochlorite. SETTINGS AND DESIGN REGISTRATION: This systematic review was registered with PROSPERO (2018 CRD42018112837) METHODS AND MATERIAL: This review was done in conformation to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA 2020) statement. In vivo studies using at least one natural irrigant and sodium hypochlorite (NaOCl) were included. Studies using them as medicaments were excluded. PubMed, Cochrane and SCOPUS were searched. RevMan tool for Risk of Bias 2 (RoB 2) and risk-of-bias tool to assess non-randomized studies of interventions (ROBINS-I) were used. GRADEpro was used to assess certainty of evidence. RESULTS: Ten articles (6 RCTs and 4 clinical studies) on approximately 442 patients were included. Seven natural irrigants were evaluated clinically. Due to the heterogeneity, meta-analysis could not be conducted. Antimicrobial efficacy was found to be similar for castor oil, neem, garlic-lemon, noni, papaine and NaOCl. Neem, papaine-chloramine, neem-NaOCl and neem-CHX were superior, while propolis, miswak and garlic were inferior to NaOCl. Post-operative pain was less for neem. There was no significant difference between papaine-chloramine, garlic extract and sodium hypochlorite in clinical/radiographic success. CONCLUSIONS: The studied natural irrigants are not more efficacious than NaOCl. At the moment, they cannot replace NaOCl routinely and may only substitute in select cases. © 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

This systematic review aimed to compare the efficacy of herbal agents with ethylene diamine tetraacetic acid (EDTA) in removing the smear layer during root canal instrumentation. The research question in the present study was to assess: "Is there a significant difference in reducing smear layer comparing EDTA and herbal agents?" Electronic databases (PubMed, Scopus, and Web of Science) were searched from their start dates to April 2022 using strict inclusion and exclusion criteria, and reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Only in vitro studies comparing herbal agents with EDTA were included in the current systematic review. Two reviewers independently assessed the included articles. A total of 625 articles were obtained from an electronic database. Eighteen papers were included for review of the full text, out of which, ten papers were excluded because they did not meet the inclusion criteria. Finally, eight articles were included in the systematic review. The present systematic review considered only in vitro studies; hence, the result cannot be completely translated to strict clinical conditions. The results of the present systematic review have shown that quixabeira, morindacitrifolia, oregano extract, and neem show better smear layer removal compared to other herbal agents, whereas they showed reduced smear layer removal when compared with EDTA. Although, it was seen that most of the included studies did not report a high quality of evidence. Hence, the present systematic review concludes that herbal agents have reported to show inferior smear layer removal when compared to EDTA. Thus, as far as herbal based alternatives are concerned, there is no highest level of evidence to state its real benefit when used as a chelating root canal irrigant.

Tungiasis (sand flea disease) is an epidermal parasitic skin disease occurring in resource-limited communities. There is no standard treatment for tungiasis, and available treatment options are scarce. To our knowledge, this is the first systematic review aimed to assess randomised controlled trials (RCTs) investigating interventions for tungiasis. We systematically searched databases including MEDLINE (EBSCOhost), CENTRAL, CINAHL, PubMed, Web of Science, SciELO, LILACS and Embase (Scopus) for RCTs in any language, from inception of the databases until June 12, 2021. RCTs exploring preventive and therapeutic interventions for tungiasis were eligible. We used the revised Cochrane Collaboration's risk of bias tool to assess the risk of bias and Jadad scale to quantify the methodological quality of the RCTs. Of the 1839 identified records, only eight RCTs involving 808 participants were included, and several methodological deficiencies were identified in most of the trials. Trial interventions included: oral drugs niridazole and ivermectin and topical interventions of ivermectin lotion, metrifonate lotion, thiabendazole lotion, thiabendazole ointment, dimeticones (NYDA), and a neem seed and coconut oils-based mixture for treatment and coconut oil-based lotion (Zanzarin) for prevention. The coconut oil-based lotion for prevention and dimeticones for treatment of tungiasis have displayed the most promise. Most of the RCTs included in this study had low methodological quality. There is a clear unmet need for high-quality RCTs examining safe and effective prevention and treatment alternatives of tungiasis in endemic settings.

OBJECTIVES: The neem (Azadirachta indica) have been used in herbal medicine for the treatment of multiple diseases, particularly cancer. The mechanism of anti-cancer properties of neem are far from clear. However, it is well accepted that anti-cancer effects of neem is mediated via its hepatic anti-oxidant activity. In the present review, we are going to classify in vitro and in vivo studies about anti-cancer activity of neem via its hepatic anti-oxidant activity. We also summarize its active ingredients and some therapeutic and toxic dosage forms. METHODS: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for neem, A. indica, anti-cancer, anti-tumor, carcinogen, liver, antioxidant activity, neem ingredients, and glutathione. Electronic database searches combined and duplicates were removed. RESULTS: The neem plant have been used in herbal medicine for the treatment of various diseases, particularly cancer. The mechanisms of anti-cancer effects of neem are far from clear. Cancerous cells growth can induce imbalance the oxidant and anti-oxidant activity in various organs particularly in the liver. Therefore, it seems that neem have anti-cancer effects via restore of the antioxidant disturbances close to the control ones in the liver. Additionally, administration of neem extract can induce oncostatic potential via several mechanism including; suppression of the NF-κβ pathway, increased expression of tumor suppressor (such as p53 and pTEN), decreased expression of oncogenes (such as c-Myc), and increased apoptosis in cancerous cells. The median lethal dose (LD50) value for extracts of neem was higher than 2,500 mg/kg. CONCLUSIONS: It is suggested that neem plays pivotal role in the prevention and treatment of cancer via its hepatic antioxidant activity. Indeed, application of neem extract can decreased tumor growth via restore of the antioxidant disturbances close to the control ones in the liver. © 2021 Walter de Gruyter GmbH, Berlin/Boston.

BACKGROUND: COVID-19 infection poses a serious risk to patients and - due to its contagious nature - to those healthcare workers (HCWs) treating them. If the mouth and nose of patients with infection are irrigated with antimicrobial solutions, this may help the patients by killing any coronavirus present at those sites. It may also reduce the risk of the active infection being passed to HCWs through droplet transmission or direct contact. However, the use of such antimicrobial solutions may be associated with harms related to the toxicity of the solutions themselves or alterations in the natural microbial flora of the mouth or nose. OBJECTIVES: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to patients with suspected or confirmed COVID-19 infection to both the patients and the HCWs caring for them. SEARCH METHODS: Information Specialists from Cochrane ENT and Cochrane Oral Health searched the Central Register of Controlled Trials (CENTRAL 2020, Issue 6); Ovid MEDLINE; Ovid Embase and additional sources for published and unpublished trials. The date of the search was 1 June 2020. SELECTION CRITERIA: This is a question that urgently requires evidence, however at the present time we did not anticipate finding many completed RCTs. We therefore planned to include the following types of studies: randomised controlled trials (RCTs); quasi-RCTs; non-randomised controlled trials; prospective cohort studies; retrospective cohort studies; cross-sectional studies; controlled before-and-after studies. We set no minimum duration for the studies. We sought studies comparing antimicrobial mouthwash and/or nasal spray (alone or in combination) at any concentration, delivered with any frequency or dosage to suspected/confirmed COVID-19 patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Our primary outcomes were: 1) RECOVERY* (www.recoverytrial.net) outcomes in patients (mortality; hospitalisation status; use of ventilation; use of renal dialysis or haemofiltration); 2) incidence of symptomatic or test-positive COVID-19 infection in HCWs; 3) significant adverse event: anosmia (or disturbance in