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Fruits and vegetables are used not only for nutritional purposes but also as therapeutics to treat various diseases and ailments. These food items are prominent sources of phytochemicals that exhibit chemopreventive and therapeutic effects against several diseases. Hirsutine (HSN) is a naturally occurring indole alkaloid found in various Uncaria species and has a multitude of therapeutic benefits. It is found in foodstuffs such as fish, seafood, meat, poultry, dairy, and some grain products among other things. In addition, it is present in fruits and vegetables including corn, cauliflower, mushrooms, potatoes, bamboo shoots, bananas, cantaloupe, and citrus fruits. The primary emphasis of this study is to summarize the pharmacological activities and the underlying mechanisms of HSN against different diseases, as well as the biopharmaceutical features. For this, data were collected (up to date as of 1 July 2023) from various reliable and authentic literature by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. Findings indicated that HSN exerts several effects in various preclinical and pharmacological experimental systems. It exhibits anti-inflammatory, antiviral, anti-diabetic, and antioxidant activities with beneficial effects in neurological and cardiovascular diseases. Our findings also indicate that HSN exerts promising anticancer potentials via several molecular mechanisms, including apoptotic cell death, induction of oxidative stress, cytotoxic effect, anti-proliferative effect, genotoxic effect, and inhibition of cancer cell migration and invasion against various cancers such as lung, breast, and antitumor effects in human T-cell leukemia. Taken all together, findings from this study show that HSN can be a promising therapeutic agent to treat various diseases including cancer.

Multidrug-resistant Acinetobacter baumannii (MDRAb), a priority-I pathogen declared by the World Health Organization, became a potential healthcare concern worldwide with a high mortality rate. Thus, the identification of putative molecular targets and potential lead molecules is an important concern in healthcare. The present study aimed to screen a prospective molecular target and effectual binders for the drug discovery of MDRAb by computational virtual screening approach. Based on the functional role, γ-carboxymuconolactone decarboxylase (CMD) was prioritized as the target and its three-dimensional (3D) structure was computationally modeled. Based on the availability of the 3D structure, twenty-five herbal molecules were selected by database search, and their drug-likeliness, pharmacokinetic, and toxicity features were predicted. The effectual binding of the selected molecules towards CMD was predicted by molecular docking. The stability of the best-docked complexes was predicted by molecular dynamics (MD) simulation for 100 ns and binding energy calculations were carried out by molecular mechanics generalized Born and surface area solvation (MM/GBSA) method. Out of twenty-five molecules screened, hirsutine (an indole alkaloid of Uncaria rhynchophylla) and thymoquinone (a phytochemical of Nigella sativa) were qualified for drug likeliness, pharmacokinetic, and toxicity features and demonstrated significant effectual binding to CMD when compared with the binding of co-crystallized inhibitor and CMD (control). The docked complexes of hirsutine and thymoquinone, and CMD were stabilized by the binding energies of −8. 30 and −8. 46 kcal/mol respectively. These molecules were qualified in terms of ideal drug likeliness, ADME, and toxicity properties. MD simulation studies showed that the ligand-protein complexes were stable throughout the simulation. The binding free energies of the complexes by MMGBSA were estimated to be −42.08157745 kcal/mol and −36.58618242 kcal/mol for hirsutine and thymoquinone respectively when compared with the calculated binding free energy of the control (−28.75032666 kcal/mol). This study concluded that hirsutine and thymoquinone can act as potential lead molecules against CMD and the present hypothesis can be scaled up to develop potential inhibitors against MDRAb. [Display omitted] •This study aimed to screen prospective molecular targets for MDR Acinetobacter baumannii.•Carboxymuconolactone decarboxylase (CMD) was prioritized as a putative target.•Two potential herbal-derived compounds were screened and they showed significant binding.•Hirsutine and thymoquinone were predicted to be effectual binders of CMD.•Natural molecules showed better effectual binding compared to CMD than co-crystallized substrate.

The bark of has been traditionally used to treat convulsion, bleeding, hypertension, auto-immune conditions, cancer, and other diseases. The main focus of this research is done for the purpose of exploring the antitumor activity and mechanism of action (MOA) for hirsutine isolated from . Jurkat clone E6-1 cells were treated using 10, 25 and 50 μM for 48 h. Inhibition of cell proliferation due to hirsutine treatment was evaluated by CCK8 assay. Flow cytometry was applied to ascertain Jurkat cell cycle progression and apoptosis after treatment with 10, 25 and 50 μM hirsutine for 48 h. The expression and level of the apoptosis-related genes and proteins was analyzed by Real-time Quantitative polymerase chain reaction (qPCR) and Western blotting method, respectively. CCK8 analyses revealed that hirsutine could significantly inhibit the proliferation of Jurkat clone E6-1 cells, in a concentration and time-dependent fashion. Flow cytometry assays revealed that hirsutine could drive apoptotic death and G0/G1 phase arrest in Jurkat cells. Apoptotic cells frequencies were 4.99 ± 0.51%, 13.69 ± 2.00% and 40.21 ± 15.19%, and respective cell cycle arrest in G0/G1 accounted for 34.85 ± 1.81%, 42.83 ± 0.70% and 49.12 ± 4.07%. Simultaneously, compared with the control group, Western blot assays indicated that the up-regulation of pro-apoptotic Bax, cleaved-caspase3, cleaved-caspase9 and Cyto c proteins, as well as the down-regulation of Bcl-2 protein which guards against cell death, might be correlated with cell death induction and inhibition of cell proliferation. QPCR analyses indicated that hirsutine could diminish expression and, at the same time, improve Bax, caspase-3 and caspase-9 mRNA levels, thus reiterating a putative correlation of hirsutine treatment in vitro with apoptosis induction and inhibition of cell proliferation ( -value < 0.05). Excessive hirsutine damages the ultrastructure in mitochondria, leading to the release of Cyt c from the mitochondria to cytoplasm in Jurkat clone E6-1 cells, thereby inducing the activated caspase cascade apoptosis process through a mitochondria-mediated pathway. An important bioactive constituent-hirsutine-appears to have antitumor effects in human T-cell leukemia, thus enlightening the use of phytomedicines as a novel source for tumor therapy. It is speculated that hirsutine may induce apoptosis of Jurkat Clone E6-1 cells through the mitochondrial apoptotic pathway.

Chronic microglial activation endangers neuronal survival through the release of various pro-inflammatory and neurotoxic factors. As such, negative regulators of microglial activation have been considered as potential therapeutic candidates to reduce the risk of neurodegeneration associated with inflammation. Uncaria rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla, has demonstrated neuroprotective potential. The aim of the present study was to examine the efficacy of HS in the repression of inflammation-induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and production of nitric oxide (NO), prostaglandin (PG) E2 and interleukin-1β. HS was demonstrated to effectively inhibit LPS-induced NO release from cultured rat brain microglia. The compound reduced the LPS-stimulated production of PGE2 and intracellular reactive oxygen species. HS significantly decreased LPS-induced phosphorylation of the mitogen-activated protein kinases and Akt signaling proteins. In conclusion, HS reduces the production of various neurotoxic factors in activated microglial cells and possesses neuroprotective activity in a model of inflammation-induced neurotoxicity.

The present authors have recently demonstrated that hirsutine, one of the major alkaloids in Uncaria species, promotes cell apoptosis by inducing DNA damage and suppresses metastasis of breast cancer cells. Despite its potent anti-cancer activity, certain types of human breast cancer cells exhibit resistance to hirsutine. To maximize the clinical utility of hirsutine therapy against breast cancer, it is critical to explore the underlying mechanism that protects hirsutine-resistant breast cancer cell lines. To identify potential targets for overcoming hirsutine-resistance, the present study investigated a library of kinase inhibitors in combination with hirsutine treatment in the hirsutine-resistant human breast carcinoma MCF-7 cell line. Amongst the 96 compounds tested, inhibitors of the ataxia telangiectasia mutated (ATM) pathway sensitized MCF-7 cells to hirsutine-induced cell death along with a sustained DNA damage response. This sensitization of MCF-7 cells to the hirsutine-induced DNA damage response by interfering with the ATM pathway did not require p53. Instead, radical oxygen species generation was significantly increased in hirsute and ATM inhibitor-treated MCF-7 cells. In conclusion, the present findings suggest the importance of the ATM pathway for optimizing the anti-cancer effect of hirsutine in breast cancer cells.

Bu çalışmada, kültürü yapılan 30 pamuk çeşidi (Gossypium hirsutum L.) arasındaki genetik ilişkinin ISSR yöntemi kullanılarak belirlenmesi hedeflenmiştir. Otuz pamuk çeşidinde polimorfizmin belirlenmesi amacıyla 24 ISSR primeri 8 pamuk çeşidinde test edilmiştir. Primerlerin yalnızca 9 tanesi PCR ürünü oluşturmuş ve sonraki çalışmalar bu primerlerle sürdürülmüştür. Seçilen 9 adet ISSR primeri 30 adet pamuk çeşidinde toplam 41 bant oluştururken bu bantlardan ortalama 22.3 tanesinin polimorfik olduğu saptanmış, primer başına polimorfik bant sayısı ortalama 2.5 olarak gerçekleşmiştir. Araştırmada kullanılan tüm primerler pamukta polimorfik bant üretirken, polimorfizm oranı primerlere bağlı olarak %6 ile %89 arasında değişim göstermiştir. ISSR primerlerine ilişkin polimorfik bilgi içeriği değerleri 0.19 ile 0.68 aralığında değişim göstermiş ve ortalama 0.49 olmuştur. Çeşitler arası ortalama Jaccard benzerlik katsayısı 0.77 olarak bulunurken, UPGMA kümeleme analiz sonucu 30 pamuk çeşidi genetik yakınlık açısından 2 ana kümeye ayrılmıştır.

Pamukta çok sayıda erkencilik özelliği kullanılmaktadır. Yatay (YÇA) ve dikey çiçeklenme aralığı (DÇA), bu özelliklerden ikisidir. Bu çalışma, YÇA ve DÇA kalıtımı (H ve h2) ile ebeveynlerin genel (GUY), melezlerin ise özel uyuşma yeteneğini (ÖUY) belirlemek amacıyla Kahramanmaraş’ta yürütülmüştür. 2010 yılında, geçci ve orta erkenci dört pamuk çeşidi ana, erkenci iki çeşit ise baba olarak kullanılmış ve Line x Tester analiz yöntemine uygun melezlemeyle sekiz F1 kombinasyonu geliştirilmiştir. 2011 yılında da ebeveynler ile melezler 26 Nisan ve 04 Haziran tarihlerinde, tesadüf blokları deneme deseninde, üç tekerrürlü ekilmiştir. Çalışma sonucunda, genotipler önemli ve özelliklerin kalıtımı yüksek bulunurken, YÇA 4.99, DÇA ise 2.86 gün olmuş ve ekim zamanı geciktikçe YÇA ortalama % -13.99, DÇA ise % -8.36 azalmıştır. Furkan ve Primera çok önemli GUY’ne sahip olurken, melezlerin ÖUY önemsiz bulunmuştur. YÇA’nın kalıtımı, ekim zamanından etkilenmemiş, DÇA kalıtımı ise geç ekimde yükselmiştir. Bu durum, eklemeli gen etkisinin yüksekliği ve üstün dominantlıktan kaynaklanırken, çok sayıda özelliğin etkilediği kütlü verimi, ekim geciktikçe ebeveynlerde % -44.39, melezlerde ise % -37.91 oranında azalmıştır.

Bu çalışmanın amacı, sulama suyunda belirli oranlarda kısıntı yaparak suyu daha verimli kullanmak ve kuraklığa toleransı yüksek pamuk genotiplerini belirlemektir. Çalışmada 7 farklı genotip (Aday 1, Aday 2, Aday 3, Aday 4, Aday 5, Aday 6 ve Aday 7) ve Stonville 468 pamuk çeşidi kullanılmıştır. Kuraklık toleransını belirlemek için Stres Duyarlılık İndeksi (SSI), Verim Kararlılık İndeksi (YSI), Verim Azalma Oranı (Yr), Verim İndeksi (YI), Toleranslılık İndeksi (TOL), Ortalama Verimlilik (MP), Harmonik Ortalama (HM), Geometrik Ortalama Verimliliği (GMP), Modifiye Edilmiş Stres Toleranslılık İndeksleri (K1STI-potansiyel verim değerlerinden elde edilerek hesaplanan indeks, K2STI- stres koşullarında elde edilen verim değerleriyle hesaplanan indeks) ve Stres Toleranslılık İndeksi (STI) kullanılmıştır. HM, MP, GMP, STI, K1STI indekslerinin stresli ve stressiz koşullarda uygulanabilirliği Aday 4 genotipinde görülmüştür. En yüksek MP değeri, Aday 6 genotipinde bulunmuştur.. En düşük SSI indeksi Aday 2’de bulunmuş ve kuraklığa toleranslı olduğunu göstermiştir. Ortalama karşılaştırma (LSD), temel bileşenler analizi (PCA) ve kümeleme (Cluster) analizi sonucunda Aday 2 genotipinin kuraklığa yüksek oranda toleranslı olduğu görülmüştür.