Plant-derived Natural Products Research Articles

Inhibitory potential of iRGD peptide-conjugated garcinol-loaded biodegradable nanoparticles in rat colorectal carcinoma

Targeted drug delivery has become attention in chemotherapy during the last decade. The principle of chemotherapy seeks maximum effect to the desired site and the minimum impact to other undesired sites of action. The nanoparticulated drug delivery system progressed a lot in this aspect in the last twenty years. Plant-derived natural products and their semisynthetic analogues boosted chemotherapy through their excellent mechanistic approach to killing cancer cells. Keeping in mind the available molecular targets in colorectal carcinoma (CRC), in this article, we proposed a peptide conjugated novel polymeric nanoparticle to deliver garcinol against colorectal carcinoma. Integrin binding peptide iRGD, sequence c(CRGDKGPDC), has been selected as a targeting moiety, as most CRC overexpress integrins. We encapsulated garcinol in biodegradable polymeric nanoparticle (PLGA)-conjugated with iRGD peptide on the particles' surface, and analyzed its (iRGD-GAR-NP's) in vitro and in vivo antineoplastic potential against CRC in a comparative way with gracinol (GAR) and garcinol-loaded PLGA nanoparticles (GAR-NP). In vitro cellular studies on human CRC cell lines, HCT116 and HT-29, revealed the superior cytotoxic potential of iRGD-GAR-NP over GAR and GAR-NP. The IC50 value on HCT116 cells was reduced by 2.3 times compared to GAR upon the application of iRGD-GAR-NP. At equivalent doses, iRGD-GAR-NP induced higher apoptosis in HCT116 cells and caused blockage of cell cycle at G0/G1 phase of the same. iRGD-GAR-NP increased the apoptotic population of HCT116 cells by 2.5 times compared to GAR. In vivo biodistribution study uncoiled the ability of GAR-NP and iRGD-GAR-NP to accumulate in the colons of dimethyl hydrazine-induced CRC-bearing Sprague-Dawely (SD) rats. In vivo antitumor efficacy study demonstrated the better effect of iRGD-GAR-NP to reduce CRC tumor progression in experimental animals. The survival rate of animals was also increased by 166% in the case of iRGD-GAR-NP compared to CRC-bearing animals received no treatment.

Preparation of Tea Aroma Precursor Glycosides: An Efficient and Sustainable Approach via Chemical Glycosidation.

Tea aroma precursor glycosides are plant-derived natural products with great economic value. However, the preparation of these glycosides remains largely overlooked in the past decades. Herein, we report a mild, efficient, and sustainable chemocatalytic procedure for the production of tea aroma precursor glycosides. During the study of the glycosidation, the catalysts were found to be decisive in the product formation favoring different reaction pathways; in addition, the influence of molecular sieves was elucidated. With regard to these findings, the serious problem of the competing orthoester formation side reaction was successfully overcome with low catalyst loading (1 mol %) and the use of 5 Å molecular sieves, leading to the preparation of a variety of tea aroma precursor β-d-glucopyranosides and β-primeverosides on a gram scale in high yields in an economical way. Taken together, the current approach features catalytic glycosidation with non-toxic and low-cost catalysts, demonstrates highly favorable greenness and sustainability, and promises industrial production of tea aroma precursor glycosides.

Cell Culture-Based Assessment of Toxicity and Therapeutics of Phytochemical Antioxidants.

Plant-derived natural products are significant resources for drug discovery and development including appreciable potentials in preventing and managing oxidative stress, making them promising candidates in cancer and other disease therapeutics. Their effects have been linked to phytochemicals such as phenolic compounds and their antioxidant activities. The abundance and complexity of these bio-constituents highlight the need for well-defined in vitro characterization and quantification of the plant extracts/preparations that can translate to in vivo effects and hopefully to clinical use. This review article seeks to provide relevant information about the applicability of cell-based assays in assessing anti-cytotoxicity of phytochemicals considering several traditional and current methods.

Endophytic Fungi: Key Insights, Emerging Prospects, and Challenges in Natural Product Drug Discovery.

Plant-associated endophytes define an important symbiotic association in nature and are established bio-reservoirs of plant-derived natural products. Endophytes colonize the internal tissues of a plant without causing any disease symptoms or apparent changes. Recently, there has been a growing interest in endophytes because of their beneficial effects on the production of novel metabolites of pharmacological significance. Studies have highlighted the socio-economic implications of endophytic fungi in agriculture, medicine, and the environment, with considerable success. Endophytic fungi-mediated biosynthesis of well-known metabolites includes taxol from Taxomyces andreanae, azadirachtin A and B from Eupenicillium parvum, vincristine from Fusarium oxysporum, and quinine from Phomopsis sp. The discovery of the billion-dollar anticancer drug taxol was a landmark in endophyte biology/research and established new paradigms for the metabolic potential of plant-associated endophytes. In addition, endophytic fungi have emerged as potential prolific producers of antimicrobials, antiseptics, and antibiotics of plant origin. Although extensively studied as a “production platform” of novel pharmacological metabolites, the molecular mechanisms of plant–endophyte dynamics remain less understood/explored for their efficient utilization in drug discovery. The emerging trends in endophytic fungi-mediated biosynthesis of novel bioactive metabolites, success stories of key pharmacological metabolites, strategies to overcome the existing challenges in endophyte biology, and future direction in endophytic fungi-based drug discovery forms the underlying theme of this article.

Construction of ajmalicine and sanguinarine de novo biosynthetic pathways using stable integration sites in yeast

Yeast cell factories have been increasingly employed for producing plant-derived natural products. Unfortunately, the stability of plant natural product biosynthetic pathway genes, particularly when driven by the same sets of promoters and terminators, remains one of the biggest concerns for synthetic biology. Here we profile genomic loci flanked by essential genes as stable integration sites in a genome-wide manner, for stable maintenance of multigene biosynthetic pathways in yeast. We demonstrate the application of our yeast integration platform in the construction of sanguinarine (24 expression cassettes) and ajmalicine (29 expression cassettes) de novo biosynthetic pathways for the first time. Moreover, we establish stable yeast cell factories that can produce 119.2 mg L-1 heteroyohimbine alkaloids (containing 61.4 mg L-1 ajmalicine) in shake flasks, representing the highest titer of monoterpene indole alkaloids (MIAs) ever reported and promising the complete biosynthesis of other high-value MIAs (such as vinblastine) for biotechnological applications.

Plant-based pharmacological alternatives in the seizure treatment: A patent review

Epilepsy, a neurologic condition associated with recurring seizures, affects around 70 million people worldwide and it is responsible for health costs. The current drug therapies used for treating epilepsy have low efficacy and many adverse side effects. In addition, drug resistance can also be found. The association of these factors considerably compromises the patient's pharmacotherapy care. Therefore, natural plant-derived products are promising therapeutic alternatives in the search for new curative options to treat epileptic seizures. Thus, the search was carried out at the patents database in the world, Espacenet, in January 2021 and compiled plant species (extracts, essential oils and isolated plant compounds) with a potential effect on the seizure, published between 2015 and 2020. In recent years, researchers and pharmaceutical companies have developed several methods for obtaining extracts, essential oils and purification of natural compounds, which have proven to be effective for the treatment of epileptic seizures in pre-clinical animal models. These findings hold potential promising for the treatment of epilepsy, especially for the management of drug-resistant, however, these reports are in their early stages and further studies need to be done for these compounds to be marketed.

Potential Mechanisms Involved in the Protective Effect of Dicaffeoylquinic Acids from Artemisia annua L. Leaves against Diabetes and Its Complications.

Diabetes mellitus is a chronic disease affecting the globe and its incidence is increasing pandemically. The use of plant-derived natural products for diabetes management is of great interest. Polar fraction of Artemisia annua L. leaves has shown antidiabetic activity in vivo. In the present study, three major compounds were isolated from this polar fraction; namely, 3,5-dicaffeoylquinic acid (1); 4,5-dicaffeoylquinic acid (2), and 3,4- dicaffeoylquinic acid methyl ester (3), using VLC-RP-18 and HPLC techniques. The potential protective effects of these compounds against diabetes and its complications were investigated by employing various in vitro enzyme inhibition assays. Furthermore, their antioxidant and wound healing effectiveness were evaluated. Results declared that these dicaffeoylquinic acids greatly inhibited DPPIV enzyme while moderately inhibited α-glucosidase enzyme, where compounds 1 and 3 displayed the most prominent effects. In addition, compound 3 showed pronounced inhibition of α-amylase enzyme. Moreover, these compounds markedly inhibited aldose reductase enzyme and exerted powerful antioxidant effects, among which compound 3 exhibited the highest activity implying a notable potentiality in impeding diabetes complications. Interestingly, compounds 2 and 3 moderately accelerated scratch wound healing. Our findings suggest that these dicaffeoylquinic acids can be promising therapeutic agents for managing diabetes and its complications.

Harmonizing biosynthesis with post-ingestive modifications to understand the ecological functions of plant natural products.

Covering: up to 2022The recent dramatic advances in our understanding of the biosynthetic pathways that produce diverse bouquets of plant-derived natural products have far surpassed our understanding of the function of these compounds for plants: how they influence a plant's Darwinian fitness in nature. Our understanding of their mechanisms, the life-processes targeted by these compounds, is similarly poorly resolved. Many plant specialized metabolites (PSMs) are further modified after ingestion by herbivores, and these post-ingestive modifications are frequently essential for PSM function. Here we summarize the biosynthesis and functional mechanisms of 17-hydroxygeranyllinalool diterpene glycosides in the ecological model plant Nicotiana attenuata, and summarize the post-ingestive modifications known from other two-component PSMs. We propose that parallel comparisons of plant natural product biosynthetic pathways and insect post-ingestive metabolism of the same plant tissues (“frassomics”) will facilitate the often-elusive identification of the molecular targets of these effective chemical defenses, contribute to elucidations of post-ingestive metabolite interactions in insect guts, and predicate the rapid evolutions of resistance against insecticides inspired by PSMs. We highlight the value of conducting these parallel investigations at the level of the entire metabolome so as to include the multiple interacting pathways in both natural product biosynthesis as well as their post-ingestive processing. We introduce the concept of frass metabolite QTL (fmQTL) analysis that integrates powerful forward genetic approaches with frassomics, and suggest that insect-guided high-throughput forward- and reverse-genetics approaches in natural habitats will advance our understanding of PSM biosynthesis and function.

L-tyrosine metabolic pathway in microorganisms and its application in the biosynthesis of plant-derived natural products

L-tyrosine, an aromatic amino acid, is an important upstream precursor for the synthesis of a series of valuable natural products such as flavonoids and phenolic acids. In recent years, regulation of the L-tyrosine metabolic pathway has been devoted to enhancing the production of L-tyrosine and the derived bioactive compounds in microorganisms, usually by increasing the supply of precursors, blocking competitive routes, and modulating the transport system. Here, we reviewed the strategies to promote L-tyrosine production in microbial hosts and the common strategies to produce bioactive compounds in engineered Escherichia coli and Saccharomyces cerevisiae to better understand and utilize the L-tyrosine metabolic pathway for microbial overproduction of diverse valuable aromatic compounds in the future.

Review on anticancer potential of Quercus infectoria and its bioactive compounds

Cancer is a life-threatening disease if not diagnosed and treated early. Available cancer treatments with undesirable side effects have led to the search for safer and more effective treatments. Therapeutic intervention using plant-derived natural products have been of great interest these days. Many plant-derived phytochemicals have been implicated with anticancer activities. Quercus infectoria is one of the prominent candidates for its chemopreventive mechanisms of action in cancer. Worldwide, this plant has been used in various medicinal purposes. Based on the available data from previous scientific researches, this review focuses on the anticancer potentials of Q. infectoria, as well as its bioactive compounds such as tannic acid, gallic acid and ellagic acid. This review will trigger of generating new insights into possible application of this plant in cancer therapy.

Current Advancements of Plant-Derived Agents for Triple-Negative Breast Cancer Therapy through Deregulating Cancer Cell Functions and Reprogramming Tumor Microenvironment.

Triple-negative breast cancer (TNBC) is defined based on the absence of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. Currently, chemotherapy is the major therapeutic approach for TNBC patients; however, poor prognosis after a standard chemotherapy regimen is still commonplace due to drug resistance. Abnormal tumor metabolism and infiltrated immune or stromal cells in the tumor microenvironment (TME) may orchestrate mammary tumor growth and metastasis or give rise to new subsets of cancer cells resistant to drug treatment. The immunosuppressive mechanisms established in the TME make cancer cell clones invulnerable to immune recognition and killing, and turn immune cells into tumor-supporting cells, hence allowing cancer growth and dissemination. Phytochemicals with the potential to change the tumor metabolism or reprogram the TME may provide opportunities to suppress cancer metastasis and/or overcome chemoresistance. Furthermore, phytochemical intervention that reprograms the TME away from favoring immunoevasion and instead towards immunosurveillance may prevent TNBC metastasis and help improve the efficacy of combination therapies as phyto-adjuvants to combat drug-resistant TNBC. In this review, we summarize current findings on selected bioactive plant-derived natural products in preclinical mouse models and/or clinical trials with focus on their immunomodulatory mechanisms in the TME and their roles in regulating tumor metabolism for TNBC prevention or therapy.

Determination of phenolic components of Vitex agnus-castus L. (Verbenaceae) from Muğla-Ula region in Turkey

Aims: In this research, it was aimed to determine the phenolic components of Vitex agnus‐castus L. (Chaste) samples belonging to Verbenaceae family, which is one of the significant medicinal plants of our country.Methods and Results: In this research, Vitex agnus-castus L. leaf and flower samples provided from during flowering grown under from Karabörtlen area (81 m) ecological conditions. Samples were then dried in a semi-shadowy and airy place at room temperature (at 25°C) to be used in the extraction process. In this study, the phenolic composition obtained from Vitex agnus-castus was analyzed and determined by UPLC-ESI-MS / MS¯ method. Totally, 8 phenolic components were determined in leaf and flower samples. Among the phenolic components of chasteberry (Vitex agnus- castus L.) obtained from leaf and flower samples during the flowering period, the most effective components; protocatechuic acid 4906.02 (mg kg¯); 4-hydroxy benzoic acid 1603.88 mg kg¯), gentisic acid 668.49 (mg kg¯) were found out.Conclusions: Plant-derived natural products have received considerable attention in recent years due to their diverse pharmacological properties, including several compounds.Most of these bioactive compounds are plant secondary metabolites such as terpenoids, alkaloids and phenolic components found in plants. Phenolic compounds as antioxidants can prevent many diseases such as cancer, heart disease, cataracts, eye diseases, old age diseases, etc. The results of this study also showed that Vitex agnus-castus leaf and flower samples, were rich in phenolic components.Significance and Impact of the Study: The results of this study indicated that Vitex agnus-castus possess a potential source of phenolics, and may be used in food, pharmaceutical and cosmetic industries as a protective agent to reduce oxidative damage in terms of phenolic components. This research can be used to guide current and future research.

Special Issue: "James D. McChesney, Vision, Passion and Leadership in the Development of Plant-Derived Natural Products".

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Anticancer efficiency of doxorubicin and berberine-loaded PCL nanofibers in preventing local breast cancer recurrence

The combination of anticancer drugs with plant-derived natural products not only enhances the cytotoxicity of chemical drugs in cancer cells but also ameliorates their toxicity in normal cells. In this study, the composite nanofibers of PCL containing anticancer drug doxorubicin (DOX) and berberine (BBR) were fabricated using the electrospinning method. The cytotoxic effects of nanofibers were evaluated on MCF-7 breast cancer cells. The drug release profile was also investigated at different pH (5.4 and 7.4). In addition, the expression levels of BCL-2 and Caspase-3 mRNA in the MCF-7 cells treated with the nanofibers were assessed by Real-Time PCR. The BBR-DOX-loaded nanofibers showed a controlled and sustained release profile in vitro up to 72 h. The loading of BBR and DOX into PCL nanofiber increased cytotoxicity in MCF-7 cells. Gene expression results also showed a significant reduction in the expression level of the BCL-2 gene in DOX-BBR-loaded nanofibers. Moreover, the treatment of cancer cells with PCL/DOX-BBR effectively increased the expression levels of the Caspase-3 gene compared to single drug-loaded nanofibers and the control group. Therefore, the dual drug-encapsulated nanofibers may be considered as a safe and promising protocol after breast cancer surgery to prevent local cancer recurrence.

Systematic identification of Ocimum sanctum sesquiterpenoid synthases and (−)-eremophilene overproduction in engineered yeast

Plant-derived natural active products have attracted increasing attention for use in flavors and perfumes. These compounds also have applications in insect pest control because of their environment-friendly properties. Holy basil (Ocimum sanctum), a famous herb used in Ayurveda in India, is a natural source of medical healing agents and insecticidal repellents. Despite the available genomic sequences and genome-wide bioinformatic analysis of terpene synthase genes, the functionality of the sesquiterpene genes involved in the unique fragrance and insecticidal activities of Holy basil are largely unknown. In this study, we systematically screened the sesquiterpenoid biosynthesis genes in this plant using a precursor-providing yeast system. The enzymes that synthesize β-caryophyllene and its close isomer α-humulene were successfully identified. The enzymatic product of OsaTPS07 was characterized by in vivo mining, in vitro reaction, and NMR detection. This product was revealed as (−)-eremophilene. We created a mutant yeast strain that can achieve a high-yield titer by adjusting the gene copy number and FPP precursor enhancement. An optimized two-stage fed-batch fermentation method achieved high biosynthetic capacity, with a titer of 34.6 g/L cyclic sesquiterpene bioproduction in a 15-L bioreactor. Further insect-repelling assays demonstrated that (−)-eremophilene repelled the insect pest, fall leafworm, suggesting the potential of (−)-eremophilene as an alternative to synthetic chemicals for agricultural pest control. This study highlights the potential of our microbial platform for the bulk mining of plant-derived ingredients and provides an impressive cornerstone for their industrial utilization.

Advances in plant-derived natural products for antitumor immunotherapy.

In recent years, immunotherapy has emerged as a novel antitumor strategy in addition to traditional surgery, radiotherapy and chemotherapy. It uniquely focuses on immune cells and immunomodulators in the tumor microenvironment and helps eliminate tumors at the root by rebuilding the immune system. Despite remarkable breakthroughs, cancer immunotherapy still faces many challenges: lack of predictable and prognostic biomarkers, adverse side effects, acquired treatment resistance, high costs, etc. Therefore, more efficacious and efficient, safer and cheaper antitumor immunomodulatory drugs have become an urgent requirement. For decades, plant-derived natural products obtained from land and sea have provided the most important source for the development of antitumor drugs. Currently, more attention is being paid to the discovery of potential cancer immunotherapy modulators from plant-derived natural products, such as polysaccharides, phenols, terpenoids, quinones and alkaloids. Some of these agents have outstanding advantages of multitargeting and low side effects and low cost compared to conventional immunotherapeutic agents. We intend to summarize the progress of comprehensive research on these plant-derived natural products and their derivatives and discuss their possible mechanisms in regulating the immune system and their efficacy as monotherapies or in combination with regular chemotherapeutic agents.

CRISPER/Cas in Plant Natural Product Research: Therapeutics as Anticancer and other Drug Candidates and Recent Patents.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR- associated9 (Cas9) endonuclease system is a facile, highly efficient and selective site-directed mutagenesis tool for RNA-guided genome-editing. CRISPR/Cas9 genome-editing strategy uses designed guide-RNAs that recognizes a 3 base-pair protospacer adjacent motif (PAM) sequence in the target-DNA. CRISPR/Cas-editing tools have mainly been employed in crop plants in relation to yield and stress tolerance. However, the immense potential of this technology has not yet been fully utilized in medicinal plants in deciphering or modulating secondary metabolic pathways producing therapeutically active phytochemicals against cancer and other diseases. The present review elucidates the use of CRISPR-Cas9 as a promising genome-editing tool in plants and plant-derived natural products with anticancer and other therapeutic applications. It also includes recent patents on the therapeutic applications of CRISPR-CAS systems implicated to cancer and other human medical conditions. Popular search engines, such as PubMed, Scopus, Google Scholar, Google Patents, Medline, ScienceDirect, SpringerLink, EMBASE, Mendeley, etc., were searched in order to retrieve literature using relevant keywords viz. CRISPER/Cas, plant natural product research, anticancer, therapeutics, etc., either singly or in various combinations. Retrieved citations and further cross-referencing among the literature have resulted in a total number of 71 publications and 3 patents are being cited in this work. Information presented in this review aims to support further biotechnological and clinical strategies to be carried using CRISPER/ Cas mediated optimization of plant natural products against cancer and an array of other human medical conditions. Off late, knock-in and knock-out, point mutation, controlled tuning of gene-expression and targeted mutagenesis have enabled the versatile CRISPR/Cas-editing device to engineer medicinal plants' genomes. In addition, by combining CRISPR/Cas-editing tool with next-generation sequencing (NGS) and various tools of system biology, many medicinal plants have been engineered genetically to optimize the production of valuable bioactive compounds of industrial significance.

Effects of Structural Manipulation on the Bioactivity of some Coumarin-Based Products.

Coumarin (2H-1-benzopyran-2-one) is a plant-derived natural product known for its pharmacological properties, such as anti-inflammatory, anticoagulant, antibacterial, antifungal, antiviral, anticancer, antihypertensive, antitubercular, anticonvulsant, antiadipogenic, antihyperglycemic, antioxidant, and neuroprotective. Two coumarin-based products were identified in the seeds of two apple phenotypes commonly known as Granny Smith and Red Delicious. This study aimed to evaluate the chemical manipulation of these coumarin-based products to more lipophilic semisynthetic compounds and trace the role of the phenolic hydroxyl group in the bioactivity of the parent natural products. The bioactivity evaluation included studying the potentials of the natural- and semisynthetic-coumarins as antioxidant, antineoplastic, antifungal, and antibacterial agents. At the first step, the antiradical potential of these products was evaluated versus the free radicals of hydroxyl and DPPH. The second potential was investigated utilizing an MTT-based photo assay versus several cancer-line cells,including SK-OV-3, MCF-7, KYSE-30, LC540, HeLa, AR42J, AB12, and AMN3. The third and fourth potentials were recognized by conducting a disc-diffusion method against six infective bacterial strains and three fungal strains. The test bacteria were Shigella dysenteriae, Klebsiella pneumonia, Escherichia coli, Haemophilus influenzae, Salmonella typhi, and Pseudomonas aeruginosa. On the other hand, the test fungi included Aspergillus flavus, Candida albicans, and Aspergillus niger. The results arising from these biopotentials revealed that the investigated functional group exerted a positive impact on the antiradical and antineoplastic potentials of the natural derivatives; however, they had a negative consequence on their antimicrobial potentials.

Traditional in vitro strategies for sustainable production of bioactive compounds and manipulation of metabolomic profile in medicinal, aromatic and ornamental plants.

Precursor feeding, elicitation and culture medium parameters are traditional in vitro strategies to enhance bioactive compounds of medicinal, aromatic, and ornamental plants (MAOPs). Machine learning can help researchers find the best combination of these strategies to increase the secondary metabolites content of MAOPs. Many requirements for human life, from food, pharmaceuticals and cosmetics to clothes, fuel and building materials depend on plant-derived natural products. Essential oils, methanolic and ethanolic extracts of in vitro undifferentiated callus and organogenic cultures of medicinal, aromatic, and ornamental plants (MAOPs) contain bioactive compounds that have several applications for various industries, including food and pharmaceutical. In vitro culture systems provide opportunities to manipulate the metabolomic profile of MAOPs. Precursors feeding, elicitation and culture media optimization are the traditional strategies to enhance in vitro accumulation of favorable bioactive compounds. The stimulation of plant defense mechanisms through biotic and abiotic elicitors is a simple way to increase the production of secondary metabolites in different in vitro culture systems. Different elicitors have been applied to stimulate defense machinery and change the metabolomic profile of MAOPs in in vitro cultures. Plant growth regulators (PGRs), stress hormones, chitosan, microbial extracts and physical stresses are the most applied elicitors in this regard. Many other chemical tolerance-enhancer additives, such as melatonin and proline, have been applied along with stress response-inducing elicitors. The use of stress-inducing materials such as PEG and NaCl activates stress tolerance elicitors with the potential of increasing secondary metabolites content of MAOPs. The present study reviewed the state-of-the-art traditional in vitro strategies to manipulate bioactive compounds of MAOPs. The objective is to provide insights to researchers involved in in vitro production of plant-derived natural compounds. The present review provided a wide range of traditional strategies to increase the accumulation of valuable bioactive compounds of MAOPs in different in vitro systems. Traditional strategies are faster, simpler, and cost-effective than other biotechnology-based breeding methods such as genetic transformation, genome editing, metabolic pathways engineering, and synthetic biology. The integrate application of precursors and elicitors along with culture media optimization and the interpretation of their interactions through machine learning algorithms could provide an excellent opportunity for large-scale in vitro production of pharmaceutical bioactive compounds.

Potential Mechanisms of Plant-Derived Natural Products in the Treatment of Cervical Cancer.

Cervical cancer is the second most common gynecological malignancy globally; it seriously endangers women’s health because of its high morbidity and mortality. Conventional treatments are prone to drug resistance, recurrence and metastasis. Therefore, there is an urgent need to develop new drugs with high efficacy and low side effects to prevent and treat cervical cancer. In recent years, plant-derived natural products have been evaluated as potential anticancer drugs that preferentially kill tumor cells without severe adverse effects. A growing number of studies have shown that natural products can achieve practical anti-cervical-cancer effects through multiple mechanisms, including inhibition of tumor-cell proliferation, induction of apoptosis, suppression of angiogenesis and telomerase activity, enhancement of immunity and reversal of multidrug resistance. This paper reviews the therapeutic effects and mechanisms of plant-derived natural products on cervical cancer and provides references for developing anti-cervical-cancer drugs with high efficacy and low side effects.