Antidiabetic Properties of Caffeoylmalic Acid, a Bioactive Natural Compound Isolated from Urtica dioica.

The uncontrolled hyperglycemia that characterizes diabetes mellitus (DM) causes several complications in the organism. DM is among the major causes of deaths, and the limited efficacy of current treatments push the search for novel drug candidates, also among natural compounds. We focused our attention on caffeoylmalic acid, a phenolic derivative extracted from Urtica dioica, a plant investigated for its potential against type 2 DM. This compound was tested for its antidiabetic activity in vitro through a glucose uptake assay, in vivo in a mouse DM model and through molecular docking towards α-amylase and α-glucosidase. The effects on glucose blood level, liver enzymes, insulin and creatinine levels as well as on lipid and blood parameters, considered biochemical markers of diabetes, were also evaluated. The results showed an antidiabetic activity in vitro and in vivo, as the compound stimulates glucose absorbtion and reduces blood glucose levels. Moreover, it ameliorates lipid profile, liver and blood parameters, with moderate effect on insulin secretion. Taken together, these findings pave the way for the compounds from this class of caffeoylmalic acid as potential antidiabetic compounds.

Anti-inflammatory and anti-diabetic properties of indanone derivative isolated from Fernandoa adenophylla in vitro and in silico studies.

Fernandoa adenophylla, due to the presence of phytochemicals, has various beneficial properties and is used in folk medicine to treat many conditions. This study aimed to isolate indanone derivative from F. adenophylla root heartwood and assess in-vitro anti-inflammatory and anti-diabetic characteristics at varying concentrations. Heat-induced hemolysis and glucose uptake by yeast cells assays were conducted to evaluate these properties. Besides, docking analyses were performed on four molecular targets. These studies were combined with molecular dynamics simulations to elucidate the time-evolving inhibitory effect of selected inhibitors within the active pockets of the target proteins (COX-1 and COX-2). Indanone derivative (10-100 µM) inhibited the lysis of human red blood cells from 9.12 ± 0.75 to 72.82 ± 4.36% and, at 5-100 µM concentrations, it significantly increased the yeast cells' glucose uptake (5.16 ± 1.28% to 76.59 ± 1.62%). Concluding, the isolated indanone might act as an anti-diabetic agent by interacting with critical amino acid residues of 5' adenosine monophosphate-activated protein kinase (AMPK), and it showed a binding affinity with anti-inflammatory targets COX-1, COX-2, and TNF-α. Besides, the obtained results may help to consider the indanone derivative isolated from F. adenophylla as a promising candidate for drug delivery, subject to outcomes of further in vivo and clinical studies.

Density functional theory, molecular docking, In vitro and In vivo anti-inflammatory investigation of lapachol isolated from Fernandoaadenophylla.

Medicinal plants are the main source of active chemical constituents responsible for curing or mitigating various ailments. To discover new, safe, and effective drug candidates the isolation and screening of natural products are essential. In the current research work, lapachol was isolated from Fernandoa adenophylla, which was evaluated for anti-inflammatory effect followed by molecular docking. The isolated compound was tested for anti-inflammatory effects using in vitro (HRBC assay) and in vivo (xylene-induced ear edema) experimental models. Various concentrations of lapachol demonstrated anti-inflammatory effects with a percent potential of 77.96 at 100 µM. Different concentrations of Lapachol demonstrated a dose-dependent anti-edematous effect with a maximum percent effect of 77.9 % at a higher dose. The histopathological study revealed that the application of xylene led to a significant increase in ear thickness, along with clear signs of ear edema and infiltration of inflammatory cells, as well as epidermal hyperplasia of the dermis when compared to the control group. However, treatment with the investigated compound showed a significant reduction in ear thickness and pathological differences comparable to those observed in the group treated with diclofenac. Density functional theory calculations are accomplished to gain insight into structural and spectroscopic properties. Geometry optimization, FMO, and MEP analyses are performed. Overall, the molecular docking results indicate that lapachol has potential as a COX inhibitor by binding to the active sites of both COX-1 and COX-2 enzymes.

In vitro anti-inflammatory, antidiabetic, antibacterial, and in silico studies of Ferruginan A isolated from Olea ferruginea Royle (Oleaceae).

Objective: Traditionally, Olea ferruginea Royle (Oleaceae) has been used as a painkiller and antidiabetic in various ailments. To provide a scientific background to this folklore the current study was designed to anti-inflammatory and antidiabetic effects of one of the isolated compound from this plant. Methods: Ferruginan A was isolated from the ethyl acetate extract of Olea ferruginea bark. This isolated molecule was subjected to in-vitro anti-inflammatory and antidiabetic effects using HRBCs and glucose uptake tests. The compound was also tested for molecular docking and ADMET study. Results: Regarding the anti-inflammatory effect, the tested compound demonstrated a 69.82 % inhibition at a concentration of 100 µg/mL, while the Ferruginan A (100 µl/mL) increased the uptake of glucose (3.79-71.86 %) in the yeast cell. Similarly, the zone of inhibition values of Ferruginan A (24.98 mm) against Escherichia coli were found to be comparable to standard (Imipenem: 31.09 mm). The mechanism of antidiabetic and anti-inflammatory effects was explored by using docking simulations performed on four molecular targets related to diabetes and inflammation. The results showed that the isolated compound may act as an antidiabetic agent by inhibiting the 5' Adenosine monophosphate-activated protein kinase (AMPK). While it also showed inhibition of anti-inflammatory targets COX-1, COX-2, and Tumor necrosis factor alpha (TNF-α). The ADMET prediction study revealed that isolated compound possesses favorable ADMET profile. Conclusion: It was concluded that Ferruginan A might be a significant anti-inflammatory and antidiabetic molecule.

Antiproliferative Activity of Lignans from Olea ferruginea: In Vitro Evidence Supported by Docking Studies.

BACKGROUND: The aim of the current study was to investigate the anticancer potential of bioactive compounds isolated from the leaves of Olea ferruginea (O. ferruginea). Lignans from O. ferruginea were previously described to possess antibacterial, antileishmanial, and antioxidant properties. Nevertheless, the antiproliferative activity of cycloolivil (1), ferruginan (2), and ferruginan A (3) have not been investigated in depth. METHODS: The compounds were isolated from the ethyl acetate fraction of the leaves extract of O. ferruginea. The isolated molecules were evaluated for their anticancer activity against U-87 MG malignant glioma cells. In parallel, molecular docking studies were also performed to investigate the interaction of the compounds with a duplex DNA sequence and epidermal growth factor receptor (EGFR). RESULTS: In vitro tests showed that all three compounds inhibit U-87 MG malignant glioma cell proliferation dose-dependently in the µM range, and ferruginan A (3) was highlighted as the most promising compound of the set. Molecular docking studies showed that the compounds could interfere with double stranded DNA possessing a cisplatin 1,2-d(GpG) intrastrand cross-link and EGFR. CONCLUSIONS: Overall, the findings suggest that the tested compounds from O. ferruginea may represent a starting point for the identification of novel tools to inhibit glioma cell proliferation.

Biological investigations of Aspergillus ficuum via in vivo, in vitro and in silico analyses.

Serious human health impacts have been observed worldwide due to several life-threatening diseases such as cancer, candidiasis, hepatic coma, and gastritis etc. Exploration of nature for the treatment of such fatal diseases is an area of immense interest for the scientific community. Based on this idea, the genus Aspergillus was selected to discover its hidden therapeutic potential. The genus Aspergillus is known to possess several biologically active compounds. The current research aimed to assess the biological and pharmacological potency of the extracts of less-studied Aspergillus ficuum (FCBP-DNA-1266) (A. ficuum) employing experimental and bioinformatics approaches. The disc diffusion method was used for the antifungal investigation, and the MTT assay was performed to assess the anticancer effects. Mice were employed as an in vivo model to evaluate the antispasmodic effects. A standard spectrophotometric technique was applied to gauge the urease inhibitory activity. The antifungal studies indicate that both n-hexane and ethyl acetate extracts were significantly active against Candida albicans (C. albicans) with their zone of inhibitions (ZOI) values reported as 19 ± 1.06 mm and 25 ± 0.55 mm, respectively at a dose of 30 µg.mL-1. In vitro cytotoxicity assay against HeLa, fibroblast 3T3, prostate PC3, and breast MCF-7 cancer cell lines was performed. The ethyl acetate extract of A. ficuum was found to be significantly active against MCF-7 with its IC50 value of 43.88 µg.mL-1. However, no substantial effects on the percent cell death of HeLa cancer cell lines were observed. In addition, the A. ficuum extracts also inhibited the urease enzyme compared to standard thiourea. The antispasmodic activity of A. ficuum extract was assessed by an in vivo model and the results demonstrated promising activity at 150 mg.kg-1. Molecular docking results also supported the antifungal, anticancer, and antiurease potency of A. ficuum extract. Overall, the results display promising aspects of A. ficuum extract as a future pharmacological source.

Insights into metabolic and pharmacological profiling of Aspergillus ficuum through bioinformatics and experimental techniques.

BACKGROUND: Recently, numerous novel bioactive fungal metabolites have been identified that possess broad therapeutic activities including anti-inflammatory, antibiotic, antioxidant, and antitumor. The fungal mycochemicals as well as extracts have increased the interest of the scientific community in drug discovery research through a combination approach such as, molecular metabolic, pharmacological and computational techniques. Therefore, the natural fungus Aspergillus ficuum (A. ficuum) (FCBP-DNA-1266) was selected for metabolic and pharmacological profiling in this study. RESULTS: The metabolic profile of A. ficuum was explored for the first time and revealed the presence of bioactive compounds such as choline sulfate, noruron, hydroxyvittatine, aurasperone D, cetrimonium, kurilensoside, heneicosane, nonadecane and eicosane. Similarly, a pharmacological screen of A. ficuum was performed for the first time in in vivo and in vitro models. Interestingly, both the ethyl acetate and n-hexane fractions of A. ficuum were found to be more active against Bacillus subtilis among five tested bacteria with their zone of inhibition (ZOI) values of 21.00 mm ±1.00 and 23.00 mm ±1.00, at a concentration of 150 µgmL-1 respectively. Similarly, a significant decrease (P<0.001) and (P<0.01) in paw edema was observed in A. ficuum-treated animals at doses of 50 and 150 mgkg-1, respectively, reflecting its potent anti-inflammatory effect. Furthermore, the docking results supported the antibacterial and anti-inflammatory effects of A. ficuum. In addition, the crude extract demonstrated no acute toxicity and the highest percent radical scavenging was recorded for both n-hexane and ethyl acetate extracts. CONCLUSION: The metabolic profile of A. ficuum indicated the presence of biological relevant compounds. A. ficuum extract exhibited potent antibacterial and anti-inflammatory effects supported by docking results. Furthermore, A. ficuum extract demonstrated the highest percentage of radical scavenging activity along with no acute toxicity.

Antioxidant and Cytotoxic Activity of a New Ferruginan A from Olea ferruginea: In Vitro and In Silico Studies.

Studies of the ethyl acetate extract bark extract of Olea ferruginea led to the isolation of one new compound Ferruginan A (1) in addition to two known compounds, Ferruginan (2) and cycloolivil (3). Structures of the isolated compounds were confirmed by mass spectrometry (MS) and NMR spectral data. The ethyl acetate fraction and compounds (1-3) were evaluated against breast cancer cell line (MCF-7) and as antioxidants using the free radical scavenging assay. Results revealed that compound 2 exhibits significant antioxidant activity with an IC50 value of 21.74 µg/mL. In addition, the ethyl acetate fraction showed good cytotoxic activity (79.31% inhibition at 250 µg/mL), whereas compounds 1-3 exerted mild cytotoxic activity (IC50 = 8.03-12.01 µg/mL) as compared to the standard (IC50 = 4.41 µg/mL) against MCF-7. Docking studies suggested that antioxidant activity is due to the chelation of compounds with copper present in the active site of tyrosinase. These results suggest that the extract exhibits considerable antioxidant activity, and the isolated compounds exert moderate anticancer activity.

Synthesis of [1-8-NαC]-zanriorb A1, alanine-containing analogues, and their cytotoxic and anti-inflammatory activity.

The synthesis of the orbitide[1-8-NαC]-zanriorb A1, isolated from the medicinal plant Zanthoxylum riedelianum, was investigated by solution-phase macrocyclization of a linear peptide and on-resin solid-phase macrocyclization with an acylsulfonamide safety-catch linker. The solution-phase route produced a mixture of proline rotamers, and the main component was assigned as the trans, cis rotamer, identical to the natural product. The on-resin cyclization was less successful, producing mainly a linear peptide, and minor cyclic products as rotameric mixtures. Although the natural product was reported to be significantly cytotoxic against Jurkat leukemia T cells, our synthetic peptides were inactive, suggesting the presence of other rotamers or impurities in the naturally isolated material. Additional analogues of zanriorb A1 were synthesized in which proline and glycine residues were replaced with alanine. While these analogues were not cytotoxic, several of them inhibited the production of nitric oxide in lipopolysaccharide (LPS)-stimulated macrophages. The most active compound, cyclic[Ala5,6,8 ]-zanriorb A1 had an IC50 of 22 µM and was more potent compared with the standard NG-monomethyl-l-arginine acetate (L-NMMA) with an IC50 of 98 µM, indicating their strong anti-inflammatory potential.

Berberine as a Potential Anticancer Agent: A Comprehensive Review.

Berberine (BBR), a potential bioactive agent, has remarkable health benefits. A substantial amount of research has been conducted to date to establish the anticancer potential of BBR. The present review consolidates salient information concerning the promising anticancer activity of this compound. The therapeutic efficacy of BBR has been reported in several studies regarding colon, breast, pancreatic, liver, oral, bone, cutaneous, prostate, intestine, and thyroid cancers. BBR prevents cancer cell proliferation by inducing apoptosis and controlling the cell cycle as well as autophagy. BBR also hinders tumor cell invasion and metastasis by down-regulating metastasis-related proteins. Moreover, BBR is also beneficial in the early stages of cancer development by lowering epithelial-mesenchymal transition protein expression. Despite its significance as a potentially promising drug candidate, there are currently no pure berberine preparations approved to treat specific ailments. Hence, this review highlights our current comprehensive knowledge of sources, extraction methods, pharmacokinetic, and pharmacodynamic profiles of berberine, as well as the proposed mechanisms of action associated with its anticancer potential. The information presented here will help provide a baseline for researchers, scientists, and drug developers regarding the use of berberine as a promising candidate in treating different types of cancers.

Myricetin: A comprehensive review on its biological potentials.

Myricetin is a critical nutritive component of diet providing immunological protection and beneficial for maintaining good health. It is found in fruits, vegetables, tea, and wine. The families Myricaceae, Polygonaceae, Primulaceae, Pinaceae, and Anacardiaceae are the richest sources of myricetin. Different researchers explored the therapeutic potential of this valuable constituent such as anticancer, antidiabetic, antiobesity, cardiovascular protection, osteoporosis protection, anti-inflammatory, and hepatoprotective. In addition to these, the compound has been tested for cancer and diabetic mellitus during clinical trials. Health benefits of myricetin are related to its impact on different cell processes, such as apoptosis, glycolysis, cell cycle, energy balance, lipid level, serum protein concentrations, and osteoclastogenesis. This review explored the potential health benefits of myricetin with a specific emphasis on its mechanism of action, considering the most updated and novel findings in the field.

Potential health benefits of carotenoid lutein: An updated review.

Carotenoids in food substances are believed to have health benefits by lowering the risk of diseases. Lutein, a carotenoid compound, is one of the essential nutrients available in green leafy vegetables (kale, broccoli, spinach, lettuce, and peas), along with other foods, such as eggs. As nutrition plays a pivotal role in maintaining human health, lutein, as a nutritional substance, confers promising benefits against numerous health issues, including neurological disorders, eye diseases, skin irritation, etc. This review describes the in-depth health beneficial effects of lutein. As yet, a minimal amount of literature has been undertaken to consider all its promising bioactivities. The step-by-step biosynthesis of lutein has also been taken into account in this review. Besides, this review demonstrates the drug interactions of lutein with ß-carotene, as well as safety concerns and dosage. The potential benefits of lutein have been assessed against neurological disorders, eye diseases, cardiac complications, microbial infections, skin irritation, bone decay, etc. Additionally, recent studies ascertained the significance of lutein nanoformulations in the amelioration of eye disorders, which are also considered in this review. Moreover, a possible approach for the use of lutein in bioactive functional foods will be discussed.

In Vivo Antinociceptive, Muscle Relaxant, Sedative, and Molecular Docking Studies of Peshawaraquinone Isolated from Fernandoa adenophylla (Wall. ex G. Don) Steenis.

Fernandoa adenophylla (Wall. ex G. Don) Steenis is traditionally used to cure various diseases and can be included as an ingredient in massage oils, which are supposed to comfort muscular tension and pain. This study was designed to assess the antinociceptive, muscle relaxant, and molecular docking properties of a novel compound, namely, (5aR,5a1R,6R,7aS,14bR,15R)15-hydroxy-7a-methyl-6-(2-methylprop-1-en-1-yl)-7,7a,14b,15-tetrahydro-5H-t-5a,15methanobenzo[g]benzo[5,6]azuleno[1,8-bc]chromene-5,9,14,16(5a1H,6H)- tetraone (peshawaraquinone), isolated from the methanolic extract of F. adenophylla in an animal model. The chemical structure of the isolated compound was elucidated using advanced spectroscopic techniques and further confirmed by XRD analysis. Compound 1 was tested against hot plate-induced noxious stimuli at various doses (2.5, 5, 10, and 15 mg/kg i.p.). The muscle relaxation potency of compound 1 was evaluated in the inclined and traction test, while the open-field test was used for the determination of sedative potential. The isolated compound was also subjected to acute toxicity analysis. The compound was then subjected to molecular docking analysis to determine the exact mechanism of action. Compound 1 demonstrated significant (p < 0.05) analgesic effect in a dose-dependent manner. A noticeable muscle relaxant effect was observed with the passage of time in both experimental models. The compound 1 showed a significant (p < 0.05) sedative effect, and in an acute toxicity study, the compound 1 was devoid of any noxious effects. The docking studies showed preferential affinity for µ-opioid and GABAA receptors. Hence, the prospective antinociceptive and muscle relaxant and sedative properties are probably mediated through these two target interactions.

Anti-inflammatory and In Silico Docking Studies of Heterophragma adenophyllum Seem Stem Constituents.

Heterophragma adenophyllum is a traditional medicinal plant that has been used as anti-inflammatory and to relief muscular tension. In the current research, four isolated constitutes namely lapacho (1), peshawaraquinone (2), indanone derivatives (3), α-lapachone (4) of H. adenophyllum were tested for anti-inflammatory effect using the carrageenan- and histamine-induced paw edema paradigm. The tested compounds (1-4) were evaluated for anti-inflammatory effect during the early and late phase of edema induction. In the early phase, all tested compounds (0.5 2.5 mg/kg each i.p.) demonstrated less than 50% effect, while in the later phase, compounds (2 and 3) demonstrated 85.66 and 89.87% attenuation. In addition, compounds (1-4) were subjected to histamine-induced inflammation, where compounds 2 and 3 exhibited excellent effects 86.87 and 89.98%, respectively at 5 mg/kg after the 2nd hour of administration, whereas compounds 1 and 4 did not exhibit any significant effect as compared with the negative control. Molecular docking results revealed a very high potency of compound based on the protein-ligand interaction (PLI) profile, which was further evaluated through a molecular dynamic simulation study. Therefore, the anti-inflammatory effect of H. adenophyllum attributed to the presence of these bioactive compounds (1-4) strongly supports the traditional uses of H. adenophyllum for treatment of inflammation. However, compounds 2 and 3 which exerted anti-inflammatory effect must be subjected for further mechanistic studies.

Chrysin: Pharmacological and therapeutic properties.

Chrysin is a promising phytochemical that is categorized under the class of flavonoids based on its chemical structure. Naturally, it is widely present in propolis, honey, passion fruit, and even in mushrooms and other plant sources, whereas its synthetic counterparts are also being employed for pharmacological purposes. It has widely been employed in treatment of various degenerative disorders and provides cytotoxic and anti-inflammatory functions. Its antioxidant and disease preventing abilities are attributed to its structural diversity arising in ring-A and absence of oxygenation in B and C ring. In this review, the scientific studies are being reported emphasizing benefits and its allied health claims on chrysin in numerous metabolic malfunctions.

The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review.

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine-sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, ß-galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep-inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]-AEA metabolism, kinases, and DNA polymerase ß1 . Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.

Potent leishmanicidal and antibacterial metabolites from Olea ferruginea.

Inspired from the leishmanicidal and antibacterial potential of the fractions obtained from the crude extract of Olea ferruginea stem, the anti-leishmanial ethyl acetate fraction was subjected to chromatographic separation, leading to the isolation of a new compound ferruginan (1) and a known compound (+)- cycloolivil (2). The structures of 1 and 2 were determined by various spectroscopic techniques and were assayed for their in vitro antibacterial and leishmanicidal potential. Compound 1 showed 75% inhibition after 24 h of incubation and 98% inhibition after 48 h of incubation against Leishmania tropica KWH23 promastigotes at 100 µg/mL concentration, while compound 2 exhibited 73% and 96% inhibition at the same concentration and incubation time. Compound 1 also showed good activity against various bacterial pathogens.

Chemo-preventive and therapeutic effect of the dietary flavonoid kaempferol: A comprehensive review.

Kaempferol, a natural flavonoid present in several plants, possesses a wide range of therapeutic properties such as antioxidant, anticancer, and anti-inflammatory. It has a significant role in reducing cancer and can act as a therapeutic agent in the treatment of diseases and ailments such as diabetes, obesity, cardiovascular diseases, oxidative stress, asthma, and microbial contamination disorders. Kaempferol acts through different mechanisms: It induces apoptosis (HeLa cervical cancer cells), decreases cell viability (G2/M phase), downregulates phosphoinositide 3-kinase (PI3K)/AKT (protein kinase B) and human T-cell leukemia/lymphoma virus-I (HTLV-I) signaling pathways, suppresses protein expression of epithelial-mesenchymal transition (EMT)-related markers including N-cadherin, E-cadherin, Slug, and Snail, and metastasis-related markers such as matrix metallopeptidase 2 (MMP-2). Accordingly, the aim of the present review is to collect information pertaining to the effective role of kaempferol against various degenerative disorders, summarize the antioxidant, anti-inflammatory, anticancer, antidiabetic, and antiaging effects of kaempferol and to review the progress of recent research and available data on kaempferol as a protective and chemotherapeutic agent against several ailments.

Phytochemical screening, antioxidant, and in vivo neuropharmacological effect of Monotheca buxifolia (Falc.) barks extract.

Owing to its pharmacological versatility, the current study focuses the evaluation of Monotheca buxifolia (M. buxifolia) bark crude extract and its fractions for phytochemical and pharmacological analysis. Phytochemical investigation of bark extract was carried out through GC-MS, LC-MS and FT-IR. ICP-OES was used for analyzing essential metals in bark extract. Plant samples were further investigated for their in vitro antioxidant and in vivo neuropharmacological activities in mice. Phytochemical analysis of bark extract revealed the presence of various active constituents such as serotonin, α-tocopherol, 3-deoxyestradiol, ascorbyl palmitate and cirsimaritin. Metal analysis showed presence of various metals in diverse concentration. M. buxifolia bark extract and its chloroform fraction showed significant antioxidant activity against DPPH (89.55 ±1.29; 84.80±1.66%), superoxide (82.10 ±1.86; 80.0±1.0%), H2O2 (80.55±2.0; 78.10±2.26%) at 500µg/mL concentration. Similarly, bark extract and its chloroform fraction demonstrated antidepressant activity in mice and improve generalized locomotive behavior. The effective use of M. buxifolia in treatment and management of depression and free radicals based disorders can be safely concluded from the results of present study.

Synthesis of breast cancer targeting conjugate of temporin-SHa analog and its effect on pro- and anti-apoptotic protein expression in MCF-7 cells.

The frog natural product temporin-SHa (FLSGIVGMLGKLFamide) is a potent antimicrobial peptide, as is the analog [S3K]SHa. By solid-phase synthesis, we prepared temporin-SHa and several temporin-SHa analogs with one or more D-alanine residues incorporated. The natural product and the analog [G10a]SHa were found to be cytotoxic in mammalian cell lines and induce cell death. To achieve selectivity, we conjugated the analog [G10a]SHa with a breast cancer targeting peptide (BCTP). The resulting peptide temporin [G10a]SHa-BCTP conjugate was selectively active against the MCF-7 breast cancer cell line with no cytotoxicity in NIH-3T3 fibroblasts. Unlike the natural product or [G10a]SHa, the conjugated peptide induced apoptosis, downregulating the expression of Bcl-2 and survivin and upregulating Bax and caspase-3.