Natural Drug Research Articles

Potential Cardiovascular Disease Treatment by Natural Drugs Targeting the HIF-1α Factor and its Pathway.

Cardiovascular diseases (CVDs) remain a key contributor to global morbidity and mortality. Being a vital regulator of hypoxia, hypoxia-inducible factor-1α (HIF-1α) is a crucial player in CVD treatment. Recently, increasing attention has been paid to the effect of natural drugs on CVDs. According to some studies, HIF-1α is a potential target for CVD treatment in traditional Chinese medicine. In this study, we describe the mechanism underlying the regulatory role of HIF-1α in CVDs and summarize 30 natural drugs and 3 formulations for CVD treatment through HIF-1α and its signaling pathway. The study provides new ideas for CVD prevention and treatment.

Drug-Eluting and Antibacterial Core-Shell Polycaprolactone/Pectin Nanofibers Containing Ti3C2Tx MXene and Medical Herbs for Wound Dressings.

Fibrous scaffolds capable of delivering natural drugs and herbs show great promise for tissue regeneration and wound care, particularly in personalized medicine. This study presents the fabrication and characterization of drug-eluting antibacterial core-shell mats composed of polycaprolactone (PCL) and pectin nanofibers produced through coaxial electrospinning. Berberine chloride (BBR), an herbal compound with antineoplastic, anti-inflammatory, antilipidemic, and antidiabetic properties, served as the model drug. Poly(vinyl alcohol) (PVA) was blended with pectin to enhance the mechanical properties of the core fibers. The shell was modified with two-dimensional Ti3C2Tx (MXene) nanosheets and subjected to covalent and ionic cross-linking. Structural analysis confirmed the successful production of bead-free fibers with diameters ranging from 160 to 350 nm, depending on composition. The PCL core fibers were uniformly coated with a pectin/PVA shell approximately 90 nm thick. The inclusion of BBR and MXene increased the fiber diameter. Drug-release kinetics, modeled by using Korsmeyer-Peppas, revealed a two-stage release mechanism. An initial burst release occurred within the first 24 h (kinetic exponent n = 1.36), followed by sustained release over 2 weeks (n = 0.48). The release mechanisms were identified as case-II relaxational release in the first stage, transitioning to quasi-Fickian diffusion in the second. Incorporating MXene into the shell further prolonged drug release. The mechanical strength of the scaffolds improved significantly by a factor of 7 and 4 in wet and dry conditions, respectively. In vitro biocompatibility assays using L929 cells demonstrated excellent cell attachment and compatibility. Additionally, antibacterial tests against Escherichia coli showed that the inclusion of MXene enhanced antibacterial activity by 30%. These results suggest that the functional biocomposite scaffolds hold the potential for developing innovative, drug-eluting wound dressings.

Synthesis of Non‐canonical Tryptophan Variants via Rh‐catalyzed C−H Functionalization of Anilines

AbstractTryptophan and its non‐canonical variants play critical roles in pharmaceutical molecules and various enzymes. Facile access to this privileged class of amino acids from readily available building blocks remains a long‐standing challenge. Here, we report a regioselective synthesis of non‐canonical tryptophans bearing C4−C7 substituents via Rh‐catalyzed annulation between structurally diverse tert‐butyloxycarbonyl (Boc)‐protected anilines and alkynyl chlorides readily prepared from amino acid building blocks. This transformation harnesses Boc‐directed C−H metalation and demetalation to afford a wide range of C2‐unsubstituted indole products in a redox‐neutral fashion. This umpolung approach compared to the classic Larock indole synthesis offers a novel mechanism for heteroarene annulation and will be useful for the synthesis of natural products and drug molecules containing non‐canonical tryptophan residues in a highly regioselective manner.

Phytoactive drugs used in the treatment of Alzheimer's disease and dementia.

The prevalence of Alzheimer's disease and other forms of dementia is increasing worldwide, and finding effective treatments for these conditions is a major public health challenge. Natural bioactive drugs have been identified as a promising source of potential treatments, due to their ability to target multiple pathways and their low toxicity. This paper reviews the current state of research on natural bioactive drugs used in the treatment of Alzheimer's disease and other dementias. The paper summarizes the findings of studies on various natural compounds, including curcumin, resveratrol, caffeine, genistein, quercetin, GinkoBiloba, Withaniasomnifera, Ginseng Brahmi, Giloy, and huperzine, and their effects on cognitive function, neuroinflammation, and amyloid-beta accumulation. In this review, we discuss the mechanism of action involved in the treatment of Alzheimer's disease. The paper also discusses the challenges associated with developing natural bioactive drugs for dementia treatment, including issues related to bioavailability and standardization. Finally, the paper suggests directions for future research in this area, including the need for more rigorous clinical trials and the development of novel delivery systems to improve the efficacy of natural bioactive drugs. Overall, this review highlights the potential of natural bioactive drugs as a promising avenue for the development of safe and effective treatments for Alzheimer's disease and other dementias.

Encapsulation of a 5FU-curcumin hybrid on bacterial nanocellulose for colorectal cancer treatment

The traditional treatment of colorectal cancer (CRC) involves a combination of chemotherapy and synthetic and natural drugs. In this study, a hybrid compound of 5-fluorouracil-curcumin encapsulated in bacterial nanocellulose (BNC) was evaluated for CRC treatment. Bacterial nanocellulose was produced using K. medellinensis and spray-dried. The encapsulation technique involved solvent evaporation. The interactions between cellulose and the hybrid were evaluated using adsorption isotherms and kinetics, and the system was morphologically and physiochemically characterized. The capsules were tested in vitro using Dukes' C and B CRC cells. The results indicated heterogeneous and incomplete adsorption of the hybrid onto the active sites of cellulose. Capsules with a BNC:hybrid mass ratio of 1:1 maintained the encapsulant properties while maximizing the drug load according to desorption in simulated stomach and colon fluids, where desorption in the colon was 1.79 times greater than that in the stomach. Finally, the cancer cell inhibition results indicated that the encapsulated hybrid performed better on Dukes' C-stage cells than on Duke's B-stage cells. In this study, a new system based on a hybrid cellulose compound was proposed for CRC treatment, specifically for metastatic CRC.

DES/O microemulsion for solubilizing and delivering curcumin via the nasal administration to treat acute asthma

As a natural small molecule drug derived from turmeric, curcumin is known for its good biosafety and a range of beneficial effects, including anti-inflammatory, anti-spasmodic, antioxidant, antibacterial, anti-tumor, and neuroprotective effects. Even though, its insolubility in water and instability severely limit its bioavailability and clinical applications. The present study developed a deep eutectic solvent (DES) in oil microemulsion (DES/O-ME) system loaded with Cur for intranasal administration, aiming to enhance both the solubility and permeability of Cur to significantly increase its bioavailability. The project first constructed and screened the optimal choline chloride-based DES. Subsequently, the DES/O-ME system was prepared and optimized to achieve uniform particle size and stability using a pseudo-ternary phase diagram and electrical conductivity measurements. The resulting DES/O-ME system was thoroughly evaluated for its solubilization efficacy, permeability, mucosal cytotoxicity, and stability. Additionally, the therapeutic efficacy of the Cur-DES/O-ME was assessed in vivo using a murine model of allergic asthma. This comprehensive evaluation highlights the potential of the DES/O-ME system as a promising intranasal drug delivery platform to overcome the limitations of curcumin’s bioavailability and clinical application.

Review on Natural Agents as Aromatase Inhibitors: Management of Breast Cancer.

Breast cancer is a prevalent type of cancer that is typically hormone-dependent, caused by estrogen. Aromatase inhibitors are frequently utilised in the treatment of hormonereceptor- positive breast cancer because they prevent the enzyme aromatase from converting androgens to estrogens. Natural medicines with aromatase inhibitory characteristics have attracted interest as potential alternatives or complementary therapy to manufactured medications. This review discusses the function of natural agents as aromatase inhibitors in treating breast cancer. A variety of natural compounds have been investigated for their capacity to inhibit aromatase activity and lower estrogen levels. These agents include resveratrol from red wine and grapes, curcumin from turmeric extract and green teahigh in catechins, and other flavonoids such as genistein, luteolin and quercetin. It has been demonstrated that by decreasing estrogen synthesis, they can slow the growth of breast cancer cells that are dependent on estrogen. However, the clinical evidence supporting their efficacy and safety in breast cancer treatment is inadequate. More research is required to investigate the therapeutic potential of natural medicines, such as aromatase inhibitors, in treating breast cancer. The clinical trials are required to assess their efficacy, appropriate doses, and potential interactions with other therapies. In conclusion, natural aromatase inhibitory drugs are promising adjuncts in the treatment of hormone receptor-positive breast cancer. Their clinical value and safety profile, however, require additional investigation.

A Direct Visible‐Light Mediated Coupling Of Azaarenes with Diversely Functionalized Alkyl Carbons via Organophotocatalytic Sp3C−H Bond Activation

AbstractSubstituted azaarenes are one of the most ubiquitous moieties in natural products and drug molecules. An efficient organophotocatalytic method for direct coupling of diverse cyclic and acyclic alkyl carbons of alcohols, ethers, alkyl halides and alkanes with different azaaryl systems has been developed. It uses low loading of easily synthesizable efficient acridinium based photocatalyst and blue LED to generate highly reactive radicals on saturated hydrocarbons through sequential single electron transfer (SET) and hydrogen atom transfer (HAT) process. These in situ generated nucleophilic carbon radicals then undergo instantaneous regio‐selective coupling with azaarenes through Minisci type coupling to generate an array of important pharmacophores through sp2C−sp3C bond formation. With inexpensive organophotocatalysts, higher yield and wide substrate scope, this method provides a greener, efficient and versatile alternative to the previously reported syntheses.

Microemulsion-based topical hydrogels containing lemongrass leaf essential oil (Cymbopogon citratus (DC.) Stapf) and mango seed kernel extract (Mangifera indica Linn) for acne treatment: Preparation and in-vitro evaluations.

Current treatments for severe acne include combinations of synthetic anti-inflammatory and antibacterial drugs, which possess numerous side effects. Therefore, this study developed microemulsion-based hydrogel containing lemongrass leaf essential oil (Cymbopogon citratus (DC.) Stapf) and mango seed kernel extract (Mangifera indica Linn) as a potential natural therapy for inflammatory acne. To this end, the microemulsions were first prepared using pseudo-ternary phase diagrams with soybean oil and coconut oil, cremophor RH40, and PEG 400. The optimal formula could load 1% lemongrass oil and 10% mango extract, possessed a spherical droplet size of ~18.98 nm, a zeta potential of -5.56 mV, and a thermodynamic stability. Secondly, the microemulsion-based hydrogel was developed by simple mixing the optimal microemulsion in carbopol-940 hydrogel (3.5% w/w). The product showed a viscosity of ~3728 cPs, a pH of 5.4-6.2, a spreadability of ~24 cm, an in-vitro Franz-cell cumulative release rate of ~80% for polyphenol content and ~60% for citral within 12 h, and a good physicochemical stability of > 3 months. Thirdly, the skin compatibility/irritability of the microemulsion-based hydrogel was determined by the HET-CAM assay, which showed non-irritation level. Finally, the anti-inflammatory activities of the hydrogel, using heat-induced BSA denaturation assay and LPS-stimulated RAW 264.7 NO inhibition assay, was 4-times higher than that of the reference drug Klenzit-C® (adapalene and clindamycin gel). Moreover, the hydrogel possessed strong anti-biofilm activity in Cutibacterium acnes, comparable with Klenzit-C®. Conclusively, the microemulsion-based hydrogel containing lemongrass oil and mango seed extract demonstrated much potentials to be a promising natural drug for acne treatment.

Vibrational, theoretical characterisation and In Silico investigation of Norcinnamolaurine: a natural lead for inhibiting AURKA and overcoming immune evasion in Triple-Negative Breast Cancer

ABSTRACT Alkaloids represent a diverse category of natural compounds with noteworthy pharmacological and therapeutic applications. Benzylisoquinoline alkaloids (BIAs) are distinguished by their varied structures and potential medicinal properties. This study specifically investigates Norcinnamolaurine, a BIA found in multiple species and acknowledged for its therapeutic advantages. In the current investigation, we comprehensively analyzed Norcinnamolaurine, encompassing Frontier Molecular Orbital studies, vibrational spectroscopy, nonlinear optical properties, natural bond orbital evaluations, and Fukui's analysis. Additionally, we executed an E-pharmacophore-based screening utilizing the AURKA-Norcinnamolaurine complex. The generated hypothesis underwent database screening; lead compounds from the Natural Product and Drug Bank databases exhibited enhanced binding affinities ranging from −8.602 to −7.148 kcal/mol, demonstrating improved interactions within the AURKA binding pocket. Subsequently, the identified lead compounds were subjected to further analysis via MMGBSA, DFT, and Molecular Dynamics Simulations (MDS). Our findings indicate that Norcinnamolaurine exhibits a superior binding affinity towards the target protein. Significant outcomes were also observed in the vibrational and FMO studies. Moreover, MDS analysis revealed that the resultant complexes maintained relative stability, exhibiting minimal deviation and fluctuations. This stability was corroborated through additional assessments using MMPBSA and PCA/FEL methodologies.

N-Trifluoroethoxy Benzotriazolium Triflate: A Readily Available Reagent for Direct Radical Trifluoroethoxylation of Alkenes.

Herein, we describe the development and application of a novel benzotriazole-based reagent toward radical trifluoroethoxylation. Various alkene classes, including styrene derivatives, enol carbonates, and allyl silanes, are viable reaction partners in this transformation, yielding diverse trifluoroethoxylated products. Furthermore, this method is readily applicable for the late-stage modification of natural product and drugs molecules. Mechanistic and computational studies suggest the intermediacy of an OCH2CF3 radical generated under photocatalytic conditions.

Construction of an Innovative Nanogel and Its Applications for Achieving Chemo-Immunotherapy of Tumors.

Malignant tumors, also known as cancers, are a global public health problem. Nanogels are promising carriers for the delivery of anticancer medicines. Therefore, based on the unique microenvironment of tumor cells and the advantages of nanogels, a simple and economical one-pot synthesis method was designed to construct natural polysaccharide-based redox-responsive nanogels (LDD NGs). The enhanced permeability and retention (EPR) effect enriched LDD NGs in tumor cells, which then rapidly collapsed and released the natural antitumor drug diosgenin (DG) and the natural polysaccharide lentinan (LNT) via the depletion of a high level of reduced glutathione (GSH) in tumor cells, resulting in a synergistic therapeutic effect of chemotherapy and immunotherapy. In vivo antitumor experiments showed that LDD NGs could inhibit the proliferation and metastasis of the A549 lung cancer cells. Further studies indicated that LDD NGs could increase the production of ROS and induce apoptosis of A549 cells. In addition, LNT released from LDD NGs could promote the proliferation of dendritic cells, increase the production of NO, and upregulate the expressions of the costimulatory molecules CD40, CD80, CD86, and MHC-II. The construction of LDD NGs was a novel drug synthesis approach that could provide fresh ideas for the development of polysaccharide-based redox-responsive drug delivery systems.

Visible-light-mediated deoxygenative transformation of 1,2-dicarbonyl compounds through energy transfer process

Through the energy transfer process, mild transformations can be achieved that are often difficult to realize under thermodynamic conditions. Herein, a visible-light-driven deoxygenative coupling of 1,2-dicarbonyl compounds for C–O, C–S, and C–N bonds construction is developed via triplet state 1,2-dicarbonyls, affording a wide range of α-functionalized ketones/esters under transition-metal and external photocatalyst free conditions. The usefulness of this method is demonstrated by gram-scale synthesis, late-stage functionalization of various carboxylic acid drugs, and the synthesis of natural products and drug molecules.

Highly efficient construction of angular polycycles

Angular tricyclic and polycyclic skeletons feature typical cores in an intriguing type of natural products. We herein report the Lewis acids-catalyzed dearomative (3 + 2) cycloadditions of donor-acceptor cyclopropanes with benzene ring, by which structurally complex and diverse angular tricyclic and polycyclic carbocycles were efficiently constructed from cheap and easily available feedstock and with convenient operation. This is also the example of (3 + 2) cycloaddition of a C3-synthon with the C = C of benzene. We believe this will demonstrate its potential in the total syntheses of natural products and drug discovery.

Visible-Light-Induced α-Arylation of Ketones with (Hetero)aryl Halides.

An enamine-mediated photoredox catalyzed C(sp2)-C(sp3) cross-coupling of dual radical precursors for the arylation of ketone is presented in this Letter. These reactions led to the formation of an enamine by using pyrrolidine to functionalize the C(sp3)-H bond in ketone substrates, which could be smoothly converted to α-arylated ketones with inert aryl bromides and even aryl chlorides in moderate to good yields under mild reaction conditions. The photocatalytically induced C(sp2)-C(sp3) cross-coupling between unactivated noncyclic ketones and aryl halides was achieved, and multiple carbonyl α-arylated backbones containing various natural products and drug molecules were successfully constructed.

Hyaluronic acid-coated zein nanoparticle-mediated resveratrol therapy for the reduction of cisplatin-associated nephrotoxicity

Cisplatin (CDDP) is commonly used as an anticancer drug in clinical practice, but severe nephrotoxicity restricts it from exerting anticancer effects. Natural drugs, such as resveratrol, can alleviate the side effects of cisplatin, but their low solubility and gastrointestinal effects prevent them from working. Herein, we developed nanoparticles for kidney injury consisting of a biocompatible material, zein, as a carrier. HA-Zein/Res NPs were fabricated using low-molecular-weight hyaluronic acid coatings. This preparation is non-cytotoxic to renal tubular epithelial cells and can be used with confidence. Low-molecular-weight hyaluronic acid has inflammation-targeting properties and CDDP damage causes renal inflammation. Owing to this property of the low-molecular-weight hyaluronic acid coating, in vivo imaging experiments in mice demonstrated that the HA-Zein/Res NPs enabled more nanoparticles to accumulate in the renal sites affected by inflammation. Efficient resveratrol delivery alleviated kidney injury, and experiments demonstrated that HA-Zein/Res NPs could treat kidney injury while reducing the serum creatinine and urea nitrogen levels in mice. Collectively, these results indicated that this nanomaterial is a promising agent for reducing the clinical nephrotoxicity of cisplatin.

Endophytic Streptomyces: an underexplored source with potential for novel natural drug discovery and development.

Streptomyces has long been considered as key sources for natural compounds discovery in medicine and agriculture. These compounds have been demonstrated to possess different biological activities, including antibiotic, antifungal, anticancer, and antiviral effects. As a result, new pharmaceuticals and antibiotics have been developed. Nevertheless, there have been only a few novel discoveries of bioactive compounds in the past decades from Streptomyces in natural habitats. There is, therefore, now a renewed search for new Streptomyces species having the potential to produce many compounds from one strain in lesser explored natural habitats that may be helpful in fighting diseases. Consequently, modern genome mining approaches are imperative for discovering structurally novel natural compounds with therapeutic applications from untapped sources. In light of these facts, endophytic Streptomyces from plants may offer new avenues for the discovery of bioactive compounds with distinctive chemical properties and activities. In the present review, we present the progress made in isolating natural compounds from endophytic Streptomyces originating from plants which have remarkable antimicrobial, cytotoxic, and antifungal properties. A different of distinct structural classes of compounds were reported from endophytic Streptomyces, such as indolosequiterpene, macrolides, flavones, peptides, naphthoquinones, and terpenoids. Further, we discussed modern genomics progress in finding biosynthetic gene clusters (BGCs) encoding compounds. Overall, this review might provide valuable insights into the potential for novel drug discovery from untapped endophytic Streptomyces in the future.

Nickel-Catalyzed Cross-Electrophile Vinylation of α-Chloro Phosphonates.

Herein, we report a general and efficient Ni-catalyzed reductive cross-coupling reaction of substituted vinyl bromides and α-chloro phosphonates to access a set of α-vinyl phosphonates using zinc as the terminal reductant. This reaction exhibits broad substrate adaptability and good functional group tolerance, which allows to afford diverse compounds including structurally complex motifs from natural products and drugs. Furthermore, the practicality was certificated through the gram-scale and transformation experiments. The preliminary mechanistic investigations support a radical chain process. The potential to realize enantiomeric control makes it more valuable for further exploration.

Flavonoids against depression: a comprehensive review of literature.

Depression is a state of low mood and aversion to activity, which affects a person's thoughts, behavior, motivation, feelings, and sense of wellbeing. Pharmacologic therapies are still the best effective treatment of depression. Still, most antidepressant drugs have low efficacy and delayed onset of therapeutic action, have different side effects, and even exacerbate depression. Such conditions make it possible to look for alternatives. Consequently, we decided to summarize the impact of flavonoids on depression in this review. We searched scientific databases such as SCOPUS, PubMed, and Google Scholar to find relevant studies until July 2022. A wide variety of natural components have been shown to alleviate depression, one of which is flavonoids. Due to the growing tendency to use natural antidepressant drugs, scientific studies are increasingly being conducted on flavonoids. This study aims to review the latest scientific researches that indicate the antidepressant potential of flavonoids. Various mechanisms include neurotransmitter system modulation and dopaminergic, noradrenergic, and serotonergic pathways regulation in the central nervous system. Different compounds of flavonoids have antidepressant properties in vivo or in vitro experiments or clinical trials and can be used as alternative and complementary treatments for depression. In general, it was observed that there were no severe side effects. Our study proves the antidepressant potential of flavonoids, and considering the limited side effects, they can be used as complementary medicine for depressed patients.

Photoinduced Decarboxylative Thioacylation of N-Hydroxyphthalimide Esters with Tetraalkylthiuram Disulfides.

Dithiocarbamate is a key structural sequence in pharmaceuticals and agrochemicals, and its synthesis is crucial in organic chemistry. Although significant progress has been made in related synthesis research, developing a practical and universal synthesis method remains fascinating. Herein, we report a new visible-light-induced decarboxylation coupling reaction between N-hydroxyphthalimide esters and tetraalkylthiuram disulfides, which uses Ir(ppy)3 as a photocatalyst to promote the generation of corresponding decarboxylation thioacylation product-dithiocarbamates in high yields. This redox-neutral protocol uses inexpensive and readily available starting material under mild reaction conditions, exhibiting broad substrate scope and wide functional group compatibility. This method can be further used for post modification of complex natural products and bioactive drugs.