Comprehensive review of the repositioning of non-oncologic drugs for cancer immunotherapy.

Drug repositioning or repurposing has gained worldwide attention as a plausible way to search for novel molecules for the treatment of particular diseases or disorders. Drug repurposing essentially refers to uncovering approved or failed compounds for use in various diseases. Cancer is a deadly disease and leading cause of mortality. The search for approved non-oncologic drugs for cancer treatment involved in silico modeling, databases, and literature searches. In this review, we provide a concise account of the existing non-oncologic drug molecules and their therapeutic potential in chemotherapy. The mechanisms and modes of action of the repurposed drugs using computational techniques are also highlighted. Furthermore, we discuss potential targets, critical pathways, and highlight in detail the different challenges pertaining to drug repositioning for cancer immunotherapy.

Alkaloids as drug leads in Alzheimer's treatment: Mechanistic and therapeutic insights.

Alzheimer's disease (AD) has few effective treatment options and continues to be a major global health concern. AD is a neurodegenerative disease that typically affects elderly people. Alkaloids have potential sources for novel drug discovery due to their diverse chemical structures and pharmacological activities. Alkaloids, natural products with heterocyclic nitrogen-containing structures, are considered potential treatments for AD. This review explores the neuroprotective properties of alkaloids in AD, focusing on their ability to regulate pathways such as amyloid-beta aggregation, oxidative stress, synaptic dysfunction, tau hyperphosphorylation, and neuroinflammation. The FDA has approved alkaloids such as acetylcholinesterase inhibitors like galantamine and rivastigmine. This article explores AD's origins, current market medications, and clinical applications of alkaloids in AD therapy. This review explores the development of alkaloid-based drugs for AD, focusing on pharmacokinetics, blood-brain barrier penetration, and potential adverse effects. Future research should focus on the clinical evaluation of promising alkaloids, developing recently discovered alkaloids, and the ongoing search for novel alkaloids for medical treatment. A pharmaceutical option containing an alkaloid may potentially slow down the progression of AD while enhancing its symptoms. This review highlights the potential of alkaloids as valuable drug leads in treating AD, providing a comprehensive understanding of their mechanisms of action and therapeutic implications.

Discovery of new α-glucosides, antiglycation agent, and in silico study of 2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-3-methoxy-4H-chromen-4-one isolated from Pistacia chinensis.

Pistacia chinensis is locally practiced for treating diabetes, pain, inflammation, and erectile dysfunction. Therefore, the current studies subjected the crude extract/fractions and the isolated compound (2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-3-methoxy-4H-chromen-4-one) to α-glucosidase inhibitor and anti-glycation activities. The development of long-term complications associated with diabetes is primarily caused by chronic hyperglycemia. Regarding α-glucosidase, the most significant inhibitory effect was observed with compound 1 (93.09%), followed by the methanolic extract (80.87%) with IC50 values of 45.86 and 86.32 µM. The maximum anti-glycation potential was shown by an isolated compound 1 followed by methanolic extract with effect inhibition of 90.12 and 72.09, respectively. Compound 1 is expected to have the highest gastrointestinal absorption rate, with a predicted absorption rate of 86.156%. This indicates oral suitability. The compound 1 is expected to have no harmful effects on the liver. In addition, our docking results suggest that alpha-glucosidase and isolated compounds showed strong interaction with ILE821, GLN900, and ALA901 residues, along with a -11.95 docking score.

Green synthesis of silver and gold nanoparticles in Callistemon viminalis extracts and their antimicrobial activities.

In the current study, the bottlebrush [Callistemon viminalis (Sol. ex Gaertn.) G. Don] plant was selected for the green synthesis of silver (Ag) and gold (Au) nanoparticles and to evaluate its antibacterial and antifungal activities. Phytochemical screening of C. viminalis confirmed the presence of alkaloids, anthraquinones, saponins, tannins, betacyanins, phlobatanins, coumarins, terpenoids, steroids, glycosides, and proteins. To characterize the synthesized Ag and Au NPs, UV-Visible spectroscopy, FTIR spectroscopy for functional group identification, field emission scanning electron microscopy (FE-SEM) for particle size, and elemental analysis were performed using EDX. The UV-Visible absorption spectra of the green-synthesized Ag and Au nanoparticles were found to have a maximum absorption band at 420 nm for Ag NPs and 525 nm for Au NPs. FE-SEM analysis of the synthesized NPs revealed a circular shape with a size of 100 nm. Elemental analysis was performed for the synthesis of Ag and Au NPs, which confirmed the purity of the nanoparticles. The greenly synthesized Ag and Au NPs were also evaluated for their anti-bacterial and anti-fungal activities, which exhibited prominent inhibition activities against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Candida albicans, C. krusei, Aspergillus sp., and Trichoderma species. The highest zone of inhibition 15.5 ± 0.75 and 15 ± 0.85 mm was observed for Ag NPs against E. coli and P. aeruginosa. Similarly, Trichoderma sp. and Aspergillus sp. were inhibited by Ag NPs up to 13.5 ± 0.95 and 13 ± 0.70 mm. This work will open doors for the development of new antimicrobial agents using green chemistry.

Global status, recent trends, and knowledge mapping of olive oil research and cardiovascular disease: 50 years of investigations through bibliometric analysis.

In the Mediterranean diet, olive oil serves as the predominant fat source and has been linked to a decreased risk of mortality related to cardiovascular diseases (CVD). Still, there is no conclusive evidence correlating olive oil consumption to CVD. The aim of this study is to assess the global research, current research trends, and knowledge mapping related to the correlation between the consumption of olive oil and CVD using bibliometric analysis. On August 19, 2023, a title-specific literature search was conducted on the Scopus database using the search terms "olive oil" and "cardiovascular disease" with a date range of the past 50 years. Subsequently, bibliometric tools such as VOSviewer and Bibliometrix were employed to analyze and evaluate the obtained documents. The search yielded (n = 429) publications and showed an upward trend in the annual publication count over the last five decades. The publication number exhibited a gradual increase with a rate of 5.55%. The results also indicated that 2530 authors, 759 institutions, 47 countries, and 223 journals have publications in this research domain. The present bibliometric study will be a valuable research reference for describing the worldwide research patterns concerning the relationship between olive oil and CVD during the past 50 years. In the future, the application of olive oil for the treatment of CVDs may be an emerging research trend. Apart from this, collaborations among authors, countries, and organizations are expected.

Revisiting luteolin: An updated review on its anticancer potential.

Numerous natural products found in our diet, such as polyphenols and flavonoids, can prevent the progression of cancer. Luteolin, a natural flavone, present in significant amounts in various fruits and vegetables plays a key role as a chemopreventive agent in treating various types of cancer. By inducing apoptosis, initiating cell cycle arrest, and decreasing angiogenesis, metastasis, and cell proliferation, luteolin is used to treat cancer. Its anticancer properties are attributed to its capability to engage with multiple molecular targeted sites and modify various signaling pathways in tumor cells. Luteolin has been shown to slow the spread of cancer in breast, colorectal, lung, prostate, liver, skin, pancreatic, oral, and gastric cancer models. It exhibits antioxidant properties and can be given to patients receiving Doxorubicin (DOX) chemotherapy to prevent the development of unexpected adverse reactions in the lungs and hematopoietic system subjected to DOX. Furthermore, it could be an excellent candidate for synergistic studies to overcome drug resistance in cancer cells. Accordingly, this review covers the recent literature related to the use of luteolin against different types of cancer, along with the mechanisms of action. In addition, the review highlights luteolin as a complementary medicine for preventing and treating cancer.

In vitro and in silico antiproliferative potential of isolated flavonoids constitutes from Pistacia integerrima.

Cancer is one of the most demanding domains for innovative, effective, safe, and affordable therapeutically active chemicals. The main aim of this study is to research new phytochemicals with anticancer activity. The current experiment identified and analyzed six compounds for anti-cancer potential supported by molecular simulation studies. The defatted methanolic extract underwent column chromatography, resulting in the isolation of six flavonoids. These include 3,5,7,4'-tetrahydroxy-flavanone (1), naringenin (2), 3,5,4'-trihydroxy-7-methoxy-flavanone (3), sakuranetin (4), spinacetin (5), and patuletin (6). The isolated compounds (1-6) were assessed for in vitro anti-cancer activity against various cell lines such as HepG2 (hepatoma G2), A498 (kidney), NCI-H226 (lungs), and MDR2780AD (human ovarian). The maximum antiproliferative effect was against HepG2 and MDR2780AD. When compounds 6, 5, and 1 were compared to a standard anti-cancer medicine (paclitaxel) with an IC50 of 7.32, it was shown that compounds 6, 5, and 1 exhibited significant activity against HepG2 with IC50 values of 14.65, 20.87, and 27.09 µM, respectively. All tested compounds showed an IC50 of less than 1 µM and had notable effects against MDR2780 AD cell lines. Compound 6 exhibited notable potency against the HepG2, A498, and MDR2780AD cell lines, among the six compounds that were evaluated. In contrast, compound 3 demonstrated the most pronounced impact on the NCI-H226 cell line. Docking investigations were performed using tubulin as the specific target concerning PDB ID 4O2B. The six compounds under investigation interact hydrophobically and hydrophilically with tubulin-binding site amino acid residues.

Quantification of toxic heavy metals, trace elements and essential minerals contents in traditional herbal medicines commonly utilized in Khyber Pakhtunkhwa, Pakistan.

Traditional herbal medicines and health supplements have been empirically used to treat various disorders but most of them are not standardized and have not been experimentally validated for safety and efficacy. In the present study, various dosage forms of traditional herbal medicines prescribed for specific diseases were collected from local practitioners at different districts of Khyber Pakhtunkhwa, Pakistan. The collected samples were analyzed for heavy metal, trace elements, and minerals using atomic absorption spectroscopy. All the tested samples contained heavy metals, trace elements and minerals in different concentrations. All the samples were tested positive for the presence of toxic heavy metals such as arsenic (As), cadmium (Cd) and lead (Pb). The trace elements like cobalt (Co), iron (Fe), zinc (Zn) and chromium (Cr) were also detected in acceptable range. Similarly, the samples analyzed were rich in some of the essential minerals such as sodium (Na), magnesium (Mg) and calcium (Ca) which are necessary for the proper functioning of the body. The hazard quotient (HQ) values were measured for toxic heavy metals to determine their safe ranges for human body. The HQ values were above the permissible range for arsenic (As) in all detected samples while for cadmium (Cd) and lead (Pb), the values ware above in 50 % of the analyzed samples. The detection of toxic metals and their HQ values beyond the permissible limits in different dosage forms raised questions about their quality. This study suggests that evaluation of traditional herbal remedies for the metals contents and their standardization are strongly recommended for quality assurance and protection of public health.

Reactive oxygen species in biological systems: Pathways, associated diseases, and potential inhibitors-A review.

Reactive oxygen species (ROS) are produced under normal physiological conditions and may have beneficial and harmful effects on biological systems. ROS are involved in many physiological processes such as differentiation, proliferation, necrosis, autophagy, and apoptosis by acting as signaling molecules or regulators of transcription factors. In this case, maintaining proper cellular ROS levels is known as redox homeostasis. Oxidative stress occurs because of the imbalance between the production of ROS and antioxidant defenses. Sources of ROS include the mitochondria, auto-oxidation of glucose, and enzymatic pathways such as nicotinamide adenine dinucleotide phosphate reduced (NAD[P]H) oxidase. The possible ROS pathways are NF-κB, MAPKs, PI3K-Akt, and the Keap1-Nrf2-ARE signaling pathway. This review covers the literature pertaining to the possible ROS pathways and strategies to inhibit them. Additionally, this review summarizes the literature related to finding ROS inhibitors.

In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives.

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Density functional theory (DFT), molecular docking, and xanthine oxidase inhibitory studies of dinaphthodiospyrol S from Diospyros kaki L.

In this work, we investigated Diospyros kaki extract and an isolated compound for their potential as xanthine oxidase (XO) inhibitors, a target enzyme involved in inflammatory disorders. The prepared extract was subjected to column chromatography, and dinaphthodiospyrol S was isolated. Then XO inhibitory properties were assessed using a spectrophotometry microplate reader. DMSO was taken as a negative control, and allopurinol was used as a standard drug. The molecular docking study of the isolated compound to the XO active site was performed, followed by visualization and protein-ligand interaction. The defatted chloroform extract showed the highest inhibitory effect, followed by the chloroform extract and the isolated compound. The isolated compound exhibited significant inhibitory activity against XO with an IC50 value of 1.09 µM. Molecular docking studies showed that the compound strongly interacts with XO, forming hydrogen bond interactions with Arg149 and Cys113 and H-pi interactions with Cys116 and Leu147. The binding score of -7.678 kcal/mol further supported the potential of the isolated compound as an XO inhibitor. The quantum chemical procedures were used to study the electronic behavior of dinaphthodiospyrol S isolated from D. kaki. Frontier molecular orbital (FMO) analysis was performed to understand the distribution of electronic density, highest occupied molecular orbital HOMO, lowest unoccupied molecular orbital LUMO, and energy gaps. The values of HOMO, LUMO, and energy gap were found to be -6.39, -3.51 and 2.88 eV respectively. The FMO results indicated the intramolecular charge transfer. Moreover, reactivity descriptors were also determined to confirm the stability of the compound. The molecular electrostatic potential (MEP) investigation was done to analyze the electrophilic and nucleophilic sites within a molecule. The oxygen atoms in the compound exhibited negative potential, indicating that they are favorable sites for electrophilic attacks. The results indicate its potential as a therapeutic agent for related disorders. Further studies are needed to investigate this compound's in vivo efficacy and safety as a potential drug candidate.

Isolation and Screening of Zn (Zn) Solubilizing Rhizosphere Bacteria from Different Vegetations for Their Ability to Improve Growth, Zn Uptake, and Expression of Zn Transporter Genes in Tomato.

Zinc-solubilizing bacteria (ZSB) can convert insoluble zinc to an accessible form and increase Zn bioavailability in soil, which helps mitigate Zn deficiency in crops. In this study, different bacterial strains were screened for different Zn solubilization and plant growth promotion traits. Two bacterial strains, Acinetobacter pittii DJ55 and Stenotrophomonas maltophilia DJ24, were tested for their Zn-solubilizing potential on plate media, and both showed variable levels of Zn solubilization. The results showed that the bacterial strains applied to the plants in the pot experiment caused improvements in growth parameters compared to control conditions. DJ55, when applied with an insoluble source, enhanced plant height, leaf number, and leaf area compared to DJ24 and control conditions, while the maximum fruit weight was noticed in plants treated with ZnSO4. An increase in chlorophyll contents was noted in plants treated with ZnSO4, while maximum carotenoid contents were observed in plants treated with DJ55 + ZnO when compared with their controls. Plants supplemented with ZnO and DJ55 showed higher zinc content and iron content as compared to their respective controls. The expression patterns of the SLZIP5 and SLZIP4 genes were changed in the root and shoot. Application of ZnO stimulates both gene expression and protein synthesis in tomato roots and shoots. Inoculation of tomato plants with ZSB and insoluble ZnO reduced the expression of the SLZIP5 and SLZIP4 genes in the root and shoot. In conclusion, both strains can be considered as potential zinc-solubilizing bioinoculants to promote the growth and production yield of tomato.

Drug repurposing of FDA-approved anti-viral drugs via computational screening against novel 6M03 SARS-COVID-19.

OBJECTIVE: The COVID-19 pandemic has been recognized as severe acute respiratory syndrome, one of the worst and disastrous infectious diseases in human history. Until now, there is no cure to this contagious infection although some multinational pharmaceutical companies have synthesized the vaccines and injecting them into humans, but a drug treatment regimen is yet to come. AIM: Among the multiple areas of SARS-CoV-2 that can be targeted, protease protein has significant values due to its essential role in viral replication and life. The repurposing of FDA-approved drugs for the treatment of COVID-19 has been a critical strategy during the pandemic due to the urgency of effective therapies. The novelty in this work refers to the innovative use of existing drugs with greater safety, speed, cost-effectiveness, broad availability, and diversity in the mechanism of action that have been approved and developed for other medical conditions. METHODS: In this research work, we have engaged drug reprofiling or drug repurposing to recognize possible inhibitors of protease protein 6M03 in an instantaneous approach through computational docking studies. RESULTS: We screened 16 FDA-approved anti-viral drugs that were known for different viral infections to be tested against this contagious novel strain. Through these reprofiling studies, we come up with 5 drugs, namely, Delavirdine, Fosamprenavir, Imiquimod, Stavudine, and Zanamivir, showing excellent results with the negative binding energies in Kcal/mol as - 8.5, - 7.0, - 6.8, - 6.8, and - 6.6, respectively, in the best binding posture. In silico studies allowed us to demonstrate the potential role of these drugs against COVID-19. CONCLUSION: In our study, we also observed the nucleotide sequence of protease protein consisting of 316 amino acid residues and the influence of these pronouncing drugs over these sequences. The outcome of this research work provides researchers with a track record for carrying out further investigational procedures by applying docking simulations and in vitro and in vivo experimentation with these reprofile drugs so that a better drug can be formulated against coronavirus.

A clinical study and future prospects for bioactive compounds and semi-synthetic molecules in the therapies for Huntington's disease.

A neurodegenerative disorder (ND) refers to Huntington's disease (HD) which affects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varying degrees of neuroprotection in preclinical HD studies because of their antioxidant and anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy, and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.

Targeted therapies of curcumin focus on its therapeutic benefits in cancers and human health: Molecular signaling pathway-based approaches and future perspectives.

The curry powder spices turmeric (Curcuma longa L.), which contains curcumin (diferuloylmethane), an orange-yellow chemical. Polyphenols are the most commonly used sources of curcumin. It combats oxidative stress and inflammation in diseases, such as hyperlipidemia, metabolic syndrome, arthritis, and depression. Most of these benefits are due to their anti-inflammatory and antioxidant properties. Curcumin consumption leads to decreased bioavailability, resulting in limited absorption, quick metabolism, and quick excretion, which hinders health improvement. Numerous factors can increase its bioavailability. Piperine enhances bioavailability when combined with curcumin in a complex. When combined with other enhancing agents, curcumin has a wide spectrum of health benefits. This review evaluates the therapeutic potential of curcumin with a specific emphasis on its approach based on molecular signaling pathways. This study investigated its influence on the progression of cancer, inflammation, and many health-related mechanisms, such as cell proliferation, apoptosis, and metastasis. Curcumin has a significant potential for the prevention and treatment of various diseases. Curcumin modulates several biochemical pathways and targets involved in cancer growth. Despite its limited tissue accumulation and bioavailability when administered orally, curcumin has proven useful. This review provides an in-depth analysis of curcumin's therapeutic applications, its molecular signaling pathway-based approach, and its potential for precision medicine in cancer and human health.

Antifungal and Antiproliferative Activity of Pistagremic Acid and Flavonoids Extracted from the Galls of Pistacia chinensis subsp. integerrima.

Pistacia chinensis subsp. integerrima (J.L. Stewart) Rech. f. is a plant known for its therapeutic applications in traditional medicine, which are related to its antimicrobial, anticancer, antioxidant, anti-inflammatory, analgesic, antidiarrheal, and muscle relaxant properties. The galls of P. chinensis are rich in triterpenes and flavonoids, and we here report the extraction of pistagremic acid (1), apigenin (2) and sakuranetin (3) from this source. The isolated compounds were tested against Aspergillus flavus, Candida albicans, Candida glabrata, Fusarium solani, Microsporum canis and Trichoderma longibrachiatum. The results highlighted the antimicrobial activity of flavonoids 2 and 3, suggesting that this class of molecules may be responsible for the effect related to the traditional use. On the other hand, when the compounds and the extract were tested for their antiproliferative activity on a panel of 4 human cancer cell lines, the triterpene pistagremic acid (1) showed a higher potential, thus demonstrating a different bioactivity profile. Structure-based docking and molecular dynamics simulations were used to help the interpretation of experimental results. Taken together, the here reported findings pave the way for the rationalization of the use of P. chinensis extracts, highlighting the contributions of the different components of galls to the observed bioactivity.

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.

Agrobacterium-Mediated Genetic Transformation of Withania coagulans (Dunal) with rol A Genes and Its Antioxidant Potential.

In ancient times, Withania coagulans Dunal was used as a therapeutic plant for the treatment of several diseases. This report aims to examine the effect of Agrobacterium tumefactions-mediated transformation of W. coagulans with the rolA gene to enhance secondary metabolite production, antioxidant activity, and anticancer activity of transformed tissues. Before transgenic plant production, the authors designed an efficient methodology for in vitro transformation. In this study, leaf explants were cultured on Murashage and Skoog (MS) media containing different amounts of naphthalene acetic acid (NAA) and benzyl adenine (BA). The best performance for inducing embryogenic callus was in MS medium containing 4 µM NAA and 6.0 µM BA, while the best results for shooting (100%) were obtained at 8 µM benzyl adenine. On the other hand, direct shooting was attained by subculturing leaves on MS medium supplemented with 8 µM benzyl adenine. Prolonged shoots showed excellent in vitro rooting results (80%) with 12 µM indole-3-butyric acid (IBA). The samples were precultivated for 3 days and were followed by 48 h infection with A. tumefaciens strain GV3101 having pCV002. Then, a vector expressed the rol A gene of strain Agrobacterium rhizogenes. Furthermore, three independent transgenic shoot lines and one callus line (T2) were produced and exhibited stable integration of transgene rol A genes, as revealed by PCR analysis. Transgenic strains showed a significant increase in antioxidant potential as compared to untransformed plants. Additionally, LC-MS analysis showed that the transformed strains have a higher withanolide content as compared to untransformed ones. Moreover, the reduced proliferation of prostate cancer cells was observed after treatment with extracts of transgenic plants. Furthermore, these transformed plants exhibited superior antioxidant capability and higher withanolide content than untransformed ones. In conclusion, the reported data can be used to select withanolide-rich germplasm from transformed cell cultures.

Ethno-Dentistry of Medicinal Plants Used in North Waziristan, Pakistan.

OBJECTIVE: This study aimed at recording therapeutic plant species used by inhabitants to treat dental disorders in the district of North Waziristan, Pakistan. The indigenous people of the studied area are dependent on medicinal plants for their basic health care needs including dental care. METHODS: Ethnomedicinal data were collected using a semi-structured questionnaires, and in addition 130 local informants were interviewed. The collected data were evaluated using various quantitative indices, including use value (UV), relative frequency of citation (RFC), fidelity level (FL%), and Jaccard Index (JI). RESULTS: A total of 69 plants belonging to 48 plant families used in dental disorders were identified. The Lamiaceae was the leading family that shared 7 species, followed by Solanaceae (4 spp).The dominant life form used was herbs (47.83%), folowed by leaves (43.90%) in preparing remedies for different dental disorders. Decoction was the most common mode of preparation (34.21%), followed by pastes (21.05%). The highest RFC (0.36) was reported for Bergenia ciliata, followed by Salvadora oleoides (0.35). The majority of the plants (36 spp) were utilised as herbal medicine to treat toothache, followed by 13 species for periodontal (gum) infections, 11 species used for teeth cleaning, and 9 species for halitosis (bad breath). CONCLUSIONS: This study is the first-ever record of ethnomedicinal applications for the treatment of dental diseases from Pakistan. Some of the forgeoing hebal medications should be further evalauted for the development of pahrmaceutical bio-products for the treatment of dental disorders.