Chemical Composition of Essential Oils from Natural Populations of Artemisia scoparia Collected at Different Altitudes: Antibacterial, Mosquito Repellent, and Larvicidal Effects.

The current study aimed to evaluate the presence of chemical variations in essential oils (EOs) extracted from Artemisia scoparia growing at different altitudes and to reveal their antibacterial, mosquito larvicidal, and repellent activity. The gas chromatographic-mass spectrometric analysis of A. scoparia EOs revealed that the major compounds were capillene (9.6-31.8%), methyleugenol (0.2-26.6%), ß-myrcene (1.9-21.4%), γ-terpinene (1.5-19.4%), trans-ß-caryophyllene (0.8-12.4%), and eugenol (0.1-9.1%). The EO of A. scoparia collected from the city of Attock at low elevation was the most active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa bacteria (minimum inhibitory concentration of 156-1250 µg/mL) and showed the best mosquito larvicidal activity (LC50, 55.3 mg/L). The EOs of A. scoparia collected from the high-altitude areas of Abbottabad and Swat were the most repellent for females of Ae. aegypti and exhibited repellency for 120 min and 165 min, respectively. The results of the study reveal that different climatic conditions and altitudes have significant effects on the chemical compositions and the biological activity of essential oils extracted from the same species.

Glyoxal-derived advanced glycation end products (GO-AGEs) with UVB critically induce skin inflammaging: in vitro and in silico approaches.

Advanced glycation end products (AGEs) have potential implications on several diseases including skin inflammation and aging. AGEs formation can be triggered by several factors such as UVB, glyoxal and methylglyoxal etc. However, little attention has been paid to glyoxal-derived AGEs (GO-AGEs) and UVB-induced skin inflammaging, with none have investigated together. This study aimed to investigate the possible role of GO-AGEs and UVB in skin inflammaging focusing on revealing its molecular mechanisms. The effects of GO-AGEs in the presence or absence of UVB were studied by using enzyme linked immunosorbent assay, western blotting, qPCR, flow cytometry and in silico approaches. In HaCaT cells, GO-AGEs in the presence of UVB irradiation (125 mJ/cm2) dramatically enhanced the release of different pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) with further activation of RAGE signaling pathways (NF-κB, COX 2, and IL- 1ß) and increased oxidative stress also noticed in NHEK cells. In NHDF cells, extracellular matrix disruption noted via increasing matrix metalloproteinase release and decreasing collagen type 1 and SIRT1 expression. Besides that, the docking scores obtained from the molecular docking study support the above-mentioned results. This study strongly suggests the pivotal role of GO-AGEs in skin inflammaging and illuminates novel molecular pathways for searching most effective and updated anti-aging therapy.

Correction: Yadav et al. PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression. Pharmaceutics 2022, 14, 1326.

In the published publication [...].

Theoretical Justification of Structural, Magnetoelectronic and Optical Properties in QFeO3 (Q = Bi, P, Sb): A First-Principles Study.

One of the primary objectives of scientific research is to create state-of-the-art multiferroic (MF) materials that exhibit interconnected properties, such as piezoelectricity, magnetoelectricity, and magnetostriction, and remain functional under normal ambient temperature conditions. In this study, we employed first-principles calculations to investigate how changing pnictogen elements affect the structural, electronic, magnetic, and optical characteristics of QFeO3 (Q = Bi, P, SB). Electronic band structures reveal that BiFeO3 is a semiconductor compound; however, PFeO3 and SbFeO3 are metallic. The studied compounds are promising for spintronics, as they exhibit excellent magnetic properties. The calculated magnetic moments decreased as we replaced Bi with SB and P in BiFeO3. A red shift in the values of ε2(ω) was evident from the presented spectra as we substituted Bi with Sb and P in BiFeO3. QFeO3 (Q = Bi, P, SB) showed the maximum absorption of incident photons in the visible region. The results obtained from calculating the optical parameters suggest that these materials have a strong potential to be used in photovoltaic applications.

Essential Oil from Tagetes minuta Has Antiquorum Sensing and Antibiofilm Potential against Pseudomonas aeruginosa Strain PAO1.

Biofilms are complex communities of microorganisms that are enclosed in a matrix that shows increased resistance to antimicrobial and immunological encounters. Mostly, the traditional methods to control biofilm are exhausted; therefore, the aim is to evaluate the potential of essential oil (EO) from Tagetes minuta to encounter biofilm and other related virulence factors. The EO of T. minuta was extracted through steam-distillation, analyzed on gas chromatography-mass spectrometry, and the biofilm inhibition assays were performed with various concentrations of EO. Mainly the EO from T. minuta contains cis-ß-ocimene (29.1%), trans-tagetenone (23.1%), and cis-tagetenone (17.7%). The virulence factors were monitored while applying different concentrations of EO and it was recorded that the EO from T. minuta significantly inhibited the virulence factors linked with quorum sensing (QS), such as pyocyanin production, protease production, and swarming motility. Biofilm formation is one of the most important virulence factors associated with the QS pathway and was inhibited up to 79% in the presence of EO. Antibacterial activity against the PAO1 of EO was not so promising particularly and it has high MIC (325 µg/mL) and MBC (5000 µg/mL). EO is quite efficient to inhibit biofilm in a very small concentration of 20 µg/mL, which confirms that the biofilm inhibition by EO is not by killing bacterial cells but by inhibiting the QS pathway. The study on PAO1 constructs carrying various QS reported genes confirmed that the EO interferes with the QS pathway that ultimately controls various virulence factors caused by PAO1.

Environmental implication and cancer risk assessment of residual pollutants in cotton crop: a case study of Multan District, Pakistan.

Pakistan is the fourth largest yarn producer in the world heavily that relies on cotton crop which receives a substantial 62% of all pesticide applications. The present study was conducted to quantify the levels of pesticides such as bifenthrin, spirotetramat, pyriproxyfen, imidacloprid, and diafenthiuron in soil and plants residue at selected cotton fields of Multan District, Pakistan. In addition to pesticides, the assessment of heavy metal concentration was also conducted in order to determine the overall risks that these compounds to both plants and human population. For this analysis, 20 soil samples and 10 plant samples were collected from 10 selected cotton fields. Pesticides and heavy metals in soil and plant samples were analyzed using high-performance liquid chromatography (HPLC) and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), respectively. It was observed that all samples collected from selected fields contained pesticide residue in top soil (0-15 cm). However, no pesticides were detected in the lower soil layer (16-30 cm). In case of heavy metals, the highest concentration of Fe, Pb, and Mn was observed in both soil and plant residue samples. The heavy metals were found in the order of Fe > Mn > Pb > Zn > Cu > Cd in the soil. The total carcinogenic risk values for a few pesticides were found to range from 10-6 to 10-2, indicating that residents of the study area have low to higher chances of developing cancer. A positive correlation was observed among the pesticides (r = 0.18-0.95) as well as in metals related parameters (r = 0.49-0.96), where a weak negative correlation was found among metal to pesticide parameters except Pd where the maximum r value was 0.62. In general, the finding of this study encourages the development and adoption of sustainable agricultural practices that lower the dependence on toxic pesticides and endorse environmentally friendly alternatives.

Thymus linearis Extracts Ameliorate Indices of Metabolic Syndrome in Sprague Dawley Rats.

Materials and Methods: The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α-amylase inhibition assays, after which the protective effect of selected "hit," i.e., CE against metabolic syndrome, was determined in vivo, using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations. Results: Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant (p < 0.05) concentration of antioxidants. Satisfactory α-amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly (p < 0.05) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant (p < 0.05) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances. Conclusion: In principle, the current study's findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity.

Computational Intelligence-Based Disease Severity Identification: A Review of Multidisciplinary Domains.

Disease severity identification using computational intelligence-based approaches is gaining popularity nowadays. Artificial intelligence and deep-learning-assisted approaches are proving to be significant in the rapid and accurate diagnosis of several diseases. In addition to disease identification, these approaches have the potential to identify the severity of a disease. The problem of disease severity identification can be considered multi-class classification, where the class labels are the severity levels of the disease. Plenty of computational intelligence-based solutions have been presented by researchers for severity identification. This paper presents a comprehensive review of recent approaches for identifying disease severity levels using computational intelligence-based approaches. We followed the PRISMA guidelines and compiled several works related to the severity identification of multidisciplinary diseases of the last decade from well-known publishers, such as MDPI, Springer, IEEE, Elsevier, etc. This article is devoted toward the severity identification of two main diseases, viz. Parkinson's Disease and Diabetic Retinopathy. However, severity identification of a few other diseases, such as COVID-19, autonomic nervous system dysfunction, tuberculosis, sepsis, sleep apnea, psychosis, traumatic brain injury, breast cancer, knee osteoarthritis, and Alzheimer's disease, was also briefly covered. Each work has been carefully examined against its methodology, dataset used, and the type of disease on several performance metrics, accuracy, specificity, etc. In addition to this, we also presented a few public repositories that can be utilized to conduct research on disease severity identification. We hope that this review not only acts as a compendium but also provides insights to the researchers working on disease severity identification using computational intelligence-based approaches.

Antidepressive Effect of Natural Products and Their Derivatives Targeting BDNF-TrkB in Gut-Brain Axis.

Modern neurological approaches enable detailed studies on the pathophysiology and treatment of depression. An imbalance in the microbiota-gut-brain axis contributes to the pathogenesis of depression. This extensive review aimed to elucidate the antidepressive effects of brain-derived neurotrophic factor (BDNF)-targeting therapeutic natural products and their derivatives on the gut-brain axis. This information could facilitate the development of novel antidepressant drugs. BDNF is crucial for neuronal genesis, growth, differentiation, survival, plasticity, and synaptic transmission. Signaling via BDNF and its receptor tropomyosin receptor kinase B (TrkB) plays a vital role in the etiopathogenesis of depression and the therapeutic mechanism of antidepressants. This comprehensive review provides information to researchers and scientists for the identification of novel therapeutic approaches for neuropsychiatric disorders, especially depression and stress. Future research should aim to determine the possible causative role of BDNF-TrkB in the gut-brain axis in depression, which will require further animal and clinical research as well as the development of analytical approaches.

Neuroprotective Natural Products' Regulatory Effects on Depression via Gut-Brain Axis Targeting Tryptophan.

L-tryptophan (Trp) contributes to regulating bilateral communication of the gut-brain axis. It undergoes three major metabolic pathways, which lead to formation of kynurenine, serotonin (5-HT), and indole derivatives (under the control of the microbiota). Metabolites from the principal Trp pathway, kynurenic acid and quinolinic acid, exhibit neuroprotective activity, while picolinic acid exhibits antioxidant activity, and 5-HT modulates appetite, sleep cycle, and pain. Abnormality in Trp plays crucial roles in diseases, including depression, colitis, ulcer, and gut microbiota-related dysfunctions. To address these diseases, the use of natural products could be a favorable alternative because they are a rich source of compounds that can modulate the activity of Trp and combat various diseases through modulating different signaling pathways, including the gut microbiota, kynurenine pathway, and serotonin pathway. Alterations in the signaling cascade pathways via different phytochemicals may help us explore the deep relationships of the gut-brain axis to study neuroprotection. This review highlights the roles of natural products and their metabolites targeting Trp in different diseases. Additionally, the role of Trp metabolites in the regulation of neuroprotective and gastroprotective activities is discussed. This study compiles the literature on novel, potent neuroprotective agents and their action mechanisms in the gut-brain axis and proposes prospective future studies to identify more pharmaceuticals based on signaling pathways targeting Trp.

PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression.

Quercetin is one of the most important plant flavanols, having several pharmacological and biological uses. Quercetin (Q) is an extremely hydrophobic phytochemical and has poor intracellular absorption, which makes its use limited. Present research demonstrates that quercetin-loaded PLGA nanoparticles (PLGA-QNPs) could overcome its low hydrophilicity and improve its anti-cancer potential. PLGA nanoparticles loaded with Q were prepared by the solvent evaporation technique and its anticancer activity was examined in vitro as well as in vivo. The cell viability was assessed through MTT assay and apoptosis was assayed through Hoechst-PI and EB/AO double staining followed by mitochondrial damage through Mito-tracker RMX-Ros. Gene expression was examined through RT-PCR. Cell cycle arrest in G2/M phase was analyzed through FACS. The results obtained revealed that PLGA-QNPs significantly reduced the viability of human cervical and breast cancer cell lines. PLGA-QNPs induced apoptosis in human cervical cancer cells in a dose dependent manner. The gene expression of PI3K/AKT was down-regulated and FoxO1 was upregulated in PLGA-QNP-treated cells, which showed a high expression level of active Caspase-3 and 7, which are responsible for apoptosis. In addition, PLGA-QNPs reduced the average number of tumors and prolonged the tumor latency period in DMBA-induced mammary adenocarcinoma SD rats. These findings suggest that PLGA-QNPs inhibit cervical and breast cancer progression via mitochondrial dependent Caspase-3 and 7 and mitochondrial independent FoxO1 activation with concomitant suppression of the PI3K/AKT pathway. For future studies, we suggest that potential druggability efficacy and clinical development of anticancer PLGA-QNPs need to be evaluated intensely for successful anticancer drug development.

Corrigendum: SARS-CoV-2: Emergence of New Variants and Effectiveness of Vaccines.

[This corrects the article DOI: 10.3389/fcimb.2021.777212.].

SARS-CoV-2: Emergence of New Variants and Effectiveness of Vaccines.

The emergence of SARS-CoV-2 variants may cause resistance at the immunity level against current vaccines. Some emergent new variants have increased transmissibility, infectivity, hospitalization, and mortality. Since the administration of the first SARS-CoV-2 vaccine to a human in March 2020, there is an ongoing global race against SARS-CoV-2 to control the current pandemic situation. Spike (S) glycoprotein of SARS-CoV-2 is the main target for current vaccine development, which can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. The effectiveness of SARS-CoV-2 vaccines and other therapeutics developments are limited by the new emergent variants at the global level. We have discussed the emergent variants of SARS-CoV-2 on the efficacy of developed vaccines. Presently, most of the vaccines have been tremendously effective in severe diseases. However, there are still noteworthy challenges in certifying impartial vaccines; the stories of re-infections are generating more stressful conditions, and this needs further clinical evaluation.

Role of PARP in TNBC: Mechanism of Inhibition, Clinical Applications, and Resistance.

Triple-negative breast cancer is a combative cancer type with a highly inflated histological grade that leads to poor theragnostic value. Gene, protein, and receptor-specific targets have shown effective clinical outcomes in patients with TNBC. Cells are frequently exposed to DNA-damaging agents. DNA damage is repaired by multiple pathways; accumulations of mutations occur due to damage to one or more pathways and lead to alterations in normal cellular mechanisms, which lead to development of tumors. Advances in target-specific cancer therapies have shown significant momentum; most treatment options cause off-target toxicity and side effects on healthy tissues. PARP (poly(ADP-ribose) polymerase) is a major protein and is involved in DNA repair pathways, base excision repair (BER) mechanisms, homologous recombination (HR), and nonhomologous end-joining (NEJ) deficiency-based repair mechanisms. DNA damage repair deficits cause an increased risk of tumor formation. Inhibitors of PARP favorably kill cancer cells in BRCA-mutations. For a few years, PARPi has shown promising activity as a chemotherapeutic agent in BRCA1- or BRCA2-associated breast cancers, and in combination with chemotherapy in triple-negative breast cancer. This review covers the current results of clinical trials testing and future directions for the field of PARP inhibitor development.

Nitric Oxide as a Target for Phytochemicals in Anti-Neuroinflammatory Prevention Therapy.

Nitric oxide (NO) is a neurotransmitter that mediates the activation and inhibition of inflammatory cascades. Even though physiological NO is required for defense against various pathogens, excessive NO can trigger inflammatory signaling and cell death through reactive nitrogen species-induced oxidative stress. Excessive NO production by activated microglial cells is specifically associated with neuroinflammatory and neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis, ischemia, hypoxia, multiple sclerosis, and other afflictions of the central nervous system (CNS). Therefore, controlling excessive NO production is a desirable therapeutic strategy for managing various neuroinflammatory disorders. Recently, phytochemicals have attracted considerable attention because of their potential to counteract excessive NO production in CNS disorders. Moreover, phytochemicals and nutraceuticals are typically safe and effective. In this review, we discuss the mechanisms of NO production and its involvement in various neurological disorders, and we revisit a number of recently identified phytochemicals which may act as NO inhibitors. This review may help identify novel potent anti-inflammatory agents that can downregulate NO, specifically during neuroinflammation and neurodegeneration.

Phytochemicals against anti-diabetic complications: targeting the advanced glycation end product signaling pathway.

The role of advanced glycation end products (AGEs) is not limited to diabetes and diabetes-related complications. There are multiple modulators, including the receptor for advanced glycation end products, high mobility group box 1, glyoxalase 1, nuclear factor-kappa B, tumor necrosis factor-α, chronic unpredictable stress, reactive oxygen species, and inflammatory cytokines, which interact with AGE signaling and control diabetes, modulating these interacting modulators. The progression of diabetes, as well as related complications, can be controlled and treated. Natural products rich in bioactive constituents can interact with AGEs and their related mediators through various signaling cascades, thereby controlling and preventing the progression of diabetes. This review provides a deeper assessment of the signaling pathway, interactions between phytochemicals and AGEs, and its mediators, to develop a multifold therapeutic approach to prevent and treat diabetes and its related complications.

Correction to "Thermosensitive Chitosan-Based Injectable Hydrogel as an Efficient Anticancer Drug Carrier".

[This corrects the article DOI: 10.1021/acsomega.0c02548.].

Thermosensitive Chitosan-Based Injectable Hydrogel as an Efficient Anticancer Drug Carrier.

A thermosensitive, physically cross-linked injectable hydrogel was formulated for the effective and sustained delivery of disulfiram (DSF) to the cancer cells as there is no hydrogel formulation available until now for the delivery of DSF. As we know, hydrogels have an advantage over other drug delivery systems because of their unique properties, so we proposed to formulate an injectable hydrogel system for the sustained delivery of an anticancer drug (DSF) to cancer cells. To investigate the surface morphology, a scanning electron microscope study was carried out, and for thermal stability of hydrogels, TGA (thermogravimetric analysis) and DSC (differential scanning calorimetry) were performed. The rheological behavior of hydrogels was evaluated with the increasing temperature and time. These developed hydrogels possessing excellent biocompatibility could be injected at room temperature following rapid gel formation at body temperature. The swelling index and in vitro drug release studies were performed at different pH (6.8 and 7.4) and temperatures (25 and 37 °C). The cell viability of the blank hydrogel, free DSF solution, and Ch/DSF (chitosan/DSF)-loaded hydrogel was studied by MTT assay on SMMC-7721 cells for 24 and 48 h, which exhibited higher cytotoxicity in a dose-dependent manner in contrast to the free DSF solution. Moreover, the cellular uptake of DSF-loaded hydrogels was observed stronger as compared with free DSF. Hence, chitosan-based hydrogels loaded with DSF possessing exceptional properties can be used as a novel injectable anticancer drug for the sustained delivery of DSF for long-term cancer therapy.

Green Synthesis of Silver Nanoparticles Using Parthenium Hysterophorus: Optimization, Characterization and In Vitro Therapeutic Evaluation.

Traditional synthetic techniques for silver nanoparticles synthesis involve toxic chemicals that are harmful to humans as well as the environment. The green chemistry method for nanoparticle synthesis is rapid, eco-friendly, and less toxic as compared to the traditional methods. In the present research, we synthesized silver nanoparticles employing a green chemistry approach from Parthenium hysterophorus leaf extract. The optimized parthenium silver nanoparticles (PrSNPs) had a mean particle size of 187.87 ± 4.89 nm with a narrow size distribution of 0.226 ± 0.009 and surface charge -34 ± 3.12 mV, respectively. The physicochemical characterization of optimized SNPs was done by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Moreover, the transmission electron microscopy (TEM) analysis indicates the spherical shape of NPs with an average diameter of 20-25 nm. PrSNPs were investigated for in vitro antibacterial, antifungal, anti-inflammatory, and antioxidant properties, and showed excellent profiles. The cytotoxic activity was analyzed against two cancer cell lines, i.e., B16F10 and HepG2 for 24 h and 48 h. PrSNPs proved to be an excellent anticancer agent. These PrSNPs were also employed for the treatment of wastewater by monitoring the E. coli count, and it turned out to be reduced by 58%; hence these NPs could be used for disinfecting water. Hence, we can propose that PrSNPs could be a suitable candidate as an antimicrobial, antioxidant, anti-inflammatory, and antitumor agent for the treatment of several ailments.

A New Oleanane Type Saponin from the Aerial Parts of Nigella sativa with Anti-Oxidant and Anti-Diabetic Potential.

Natural product studies explore potential and interesting new compounds to discover innovative drugs. Nigella sativa (N. sativa) (Ranunculaceae) is traditionally used to treat diabetes. Flavonoids and triterpenoid mostly show anti-diabetic activity. The current study aim to identify new compounds by a systematic study of the anti-oxidant and anti-diabetic activity of aerial parts of N. sativa concerning. Phytochemicals were isolated from the methanolic extract of aerial parts of the plant by column chromatography and identified by nuclear magnetic resonance spectroscopy and mass spectroscopy. A new triterpenoid saponin glycoside was isolated along with flavonoids. The anti-diabetic study was carried out by DPPH, ABTS, α -glucosidase, and protein tyrosine phosphatase 1B assays at doses of 12.5 to 250 µM. The isolated phytochemicals were identified as 3-O-(ß-d-xylopyranosyl-(1-3)-α-l-rhamnopyrnaosyl-(1-2)-α-l-arabinopyranosyl]-28-O-(α-l-rhamno-pyranosyl-(1-4)-ß-d-glucopyranosyl-(1-6)-ß-d-glucopyranosyl] hederagenin (1), flaccidoside III (2), catechol (3), quercetin-3-gentiobiosides (4), magnoflorine (5), nigelflavonoside B (6), nigelloside (7), quercetin sphorotrioside (8), kaempferol-3, 7-diglucoside (9), kaempferol 3-O-rutinoside (10), rutin (11), 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsylhederagenin (12), 3ß,23,28-trihydroxyolean-12-ene-3-O-α-l-arabinopyranoside(1→4)-a-rhamnopyranosyl,(1→4)-ß-d-gluco-pyranoside (13), 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranpsyl]-28-O-ß-d-gluco-pyranosyl hederagenin (14), and α-hederin (15). These were isolated and are reported for the first time in this study. Compared 13 was identified as a new compound. Compound 2 was isolated for first time from the genus Nigella. Compound 6 was found to be the most active in the DPPH, and ABTS assays and compound 10 was found to be the most active in the α-glucosidase assay, with IC50 32.7 ± 0.1, 95.18 ± 0.9, 214.5 ± 0.0 µΜ, respectively. Compound 12, at a dose of 125 µΜ, showed anti-diabetic activity in a PTP1B assay with IC50 91.30 ± 2.5 µΜ. In conclusion, the anti-diabetic activity of N. sativa is due to its flavonoids and TTSGs. Therefore, our studies suggest that the aerial parts of N. sativa are also a valuable and alternate source of valuable phytochemicals that could be used to develop anti-oxidant and anti-diabetic medicines.