Herbal Drugs in Cancer Treatment: Current Advances, Efficacy, And Future Prospects in Modern Medicine

Abstract

Cancer remains one of the leading causes of mortality worldwide, prompting continuous exploration of effective, safe, and affordable treatment options. Herbal drugs, derived from medicinal plants, have gained increasing attention as potential therapeutic agents due to their bioactive compounds with anticancer properties. Recent advances in phytochemistry and molecular pharmacology have elucidated the mechanisms through which herbal compounds such as curcumin, resveratrol, quercetin, and berberine exert anti-proliferative, pro-apoptotic, anti-angiogenic, and immune-modulatory effects on cancer cells. Clinical and preclinical studies have shown promising results, highlighting the potential of herbal drugs to enhance the efficacy of conventional therapies and reduce treatment-associated toxicity. Despite their therapeutic promise, challenges such as variability in plant composition, lack of standardization, limited bioavailability, and regulatory hurdles remain. This review explores the current landscape of herbal drugs in cancer therapy, evaluates their clinical efficacy, and discusses future directions for integrating these natural compounds into mainstream oncological treatment, emphasizing the need for rigorous scientific validation and technological innovations to unlock their full potential.

Keywords

Introduction

1. Ginseng:
   Active Compounds: Ginsenosides

Mechanism of Action: Ginseng, particularly the Panax ginseng variety, has been used traditionally as an adaptogen. The ginsenosides have shown anti-cancer, immune-modulating [33] and anti-inflammatory actions. Ginseng increases activity of immune cells, such as natural killer (NK) cells and T-cells, to inhibit the growth of cancer cells.

Benefits: Ginseng:

Increases NK cell activity against cancer cells.
Modulates the immune system towards greater responses against tumors. Enhances the effects of chemotherapeutic and radiotherapeutic agents. [35]

Types of Cancer: Breast cancer, lung cancer, stomach cancer.

Studies: Studies have found that ginseng can result in quality of life improvement for cancer patients and can be an adjuvant therapy that enhances chemotherapy efficacy when co-administered with it, reducing side effects. [36] 

2. Boswellia (Frankincense):

Active Compound: Boswellic acids
Mechanism of Action: Boswellia, which is derived from the resin of the Boswellia tree, has anti-inflammatory [37] properties and inhibits many of those enzymes involved in inflammation and tumor growth It also causes apoptosis and blocks angiogenesis of cancer cells [38].

Benefits: Boswellia:

Reduces inflammation in tumor microenvironment potentially favoring immune responses against cancer. Inhibits cancer cell proliferation and metastasis.  Protects normal tissues from the damaging effects of chemotherapy."[39]

3. Astragalus Active Component:

Astragaloside Mechanism of Action: Astragalus is used in Traditional Chinese Medicine as a remedy for immune system support [40]. Increase in white blood cells production is essential and mainly the T cells and macrophages to attack, for the eradication of cancerous cells. It enhances the body's response to chemotherapy and radiotherapy. [41] 

Benefits: Astragalus: -Balances the immune system in order to enhance the body's response towards the disease process of cancer [42]. -Protects from the effects caused by chemotherapy and radiation therapy. -Inhibits the growth of cancer cells and prevents metastasis. [43] Types of Cancer: Lung, breast, liver, and stomach cancers. Studies: Clinical studies assert that the encouragement of general survival in cancer patients, as well as the minimization of adverse effects associated with treatment, is due to astragalus. [44]

4. Milk Thistle (Silymarin) Active Compound:

Silymarin Mechanism of Action: Silymarin is a hepatoprotective ingredient from the milk thistle plant and has been shown to exude various [45] actions such as antioxidant properties, anti-inflammatory, and anticancer effects. Such activity goes by the destruction of free radicals and diminishes the oxidative stress mechanism, which is a way of normal cancer cells in surviving. [46] 

Benefits: Silymarin: -Prevents damage to the liver resulting from chemotherapy and radiotherapy. -Induces apoptosis for cancer cells and hinders cancer cells from growing. -Modulates the signaling pathways linked to tumor progression. [47]

Herbal Drug in Combination with Conventional Therapies:

The role of medicinal herbs and their phytocompounds in cancer treatment has been recognized though slowly complementing the traditional treatment forms. An abundant number of clinical [48] studies have indicated that herbal medicines can enhance the effectiveness of conventional therapies or benefit cancer patients in survival, immune modulation, and quality of life. [49]  Several examples of clinical studies involving the use of herbal medicines in different cancers and random controlled trials in this emerging area will be reviewed here. Furthermore, some recent activities are reported on understanding the biochemical and cellular mechanisms through which herbal medicines exert their effects in specific tumor microenvironments [50] and possibilities for such use of specific phytochemicals in cell-based cancer vaccine systems. Providing such evidence-based technological support is what this review proposes for the application of herbal medicines into cancer therapy. [51]  Besides the well-characterized herbal anticancer agents, there are more new bioactive compounds that have emerged from recent studies: for example, withaferin A, a steroidal lactone[52]  derived from Withania somnifera, more popularly known as "Ashwagandha," has been shown to induce apoptosis and inhibit angiogenesis in a variety of cancer cell lines.[53] Citation48-50 Withaferin A has demonstrated excellent anticancer action in a study, inducing reactive oxygen species (ROS) that lead to apoptosis and cell proliferation inhibition in breast cancer cells.Citation48 Another study conducted by Suman et al., showed that withaferin A has a ability to sensitize ovarian cancer cells to cisplatin treatment, which indicates its possible[54]  role in the adjuvant therapy.Citation49 Another novel agent, triptolide, isolated from Tripterygium wilfordii (Thunder God Vine), exhibited induction of apoptosis and inhibition of cell growth and has potent anticancer effects[55] . Triptolide induces apoptosis in several cancer cell lines, including those of pancreatic, breast, and prostate cancer, in a manner involving multiple signaling pathways, including NF-κB, MAPK, and PI3K/Akt.Citation [56] The culmination of herbal medicines and conventional treatment has shown promise in enhancing efficacy and diminishing the side effects associated with conventional medicine [57]. For example, traditional Chinese herbal medicine used along with chemotherapy has a significantly diminishing effect when it comes to the nausea induced by chemotherapy [58]. Traditional Chinese herbal medicine may refer to a wide spectrum of herbal formulations used for centuries to combat a long list of diseases, including cancer [59]. These herbal medicines are said to harmonize with the body in restoring the balance of the infected systems with healing abilities and fortifying the defenses. Thus, the application of Traditional Chinese herbal medicine along with chemotherapy forms the complementary arm whereby both targets are the cancer and side effects of the treatment. [60] repair, apo Phytomedicines are currently involved in about sixty percent of cancer treatment strategies, and the National Cancer Institute has evaluated more than 35,000 plant species for possible anticancer activity [61], reporting that more than 3,000 have chemicals with good potential for anticancer or chemopreventive activity [62]. The bioactive compounds obtained from medicinal plants are important assets in treating cancer due to their mutual action, which has been reported in classical and conventional therapies [63]. Various phytomedicines exhibit anti-tumorigenic actions in a variety of cancers, including lung cancer [64]. An example of geofabrics is found in pharmaceuticals, for example, Ephedra alata[^] is widely used in treating lung cancer in Palestinian medicine. Another plant with therapeutic potential against lung cancer is Rhus verniciflua[65] . On the other hand, there is an indication that Rheum officinale remains a significant player among the anti-lung cancer phytomedicines. Besides, combinations of natural products with drugs have also made their appearance in clinical trials for lung cancer, particularly in the field of non-small-cell lung cancer. The drug-herb combination presents an alternative for cancer treatment owing to synergistic anticancer action, low toxicity through varied mechanisms of action [66], and widespread clinical application and promise compared to monotherapy. Combination therapy also increases the chances of survival, greatly diminishes the probability of the cancer cells developing resistance through increased cancer cell sensitivity [67], and enhanced quality of life. Phytocompounds are involved in the regulation of important pathways implicated in the initiation, progression, and metastasis of the cancer, such as the cell cycle, DNA ptosis, or cell signaling. [68]

Safety, Toxicity, And Sides Effects:

Safety Issues

Unregulated Functional Products: Many herbal products are hardly subjected to regulation by a specific government body, that is, the FDA, and because of this fact, the drug can have several dimensions,[69] one of which includes quality, purity, and safety, since most of these products may likely be contaminated with pesticides, heavy metals, or some harmful substances.[70] Interference with Conventional Therapies: Many alternative products can also interfere with chemotherapy and radiotherapy or other conventional treatments of cancer.[71] Some examples of such therapeutic effects of herbs include inhibition of the breakdown of certain chemotherapy drugs in the liver, resulting in excessive drug levels, which can increase the incidence of side effects.[72] Lack of Clinical Evidence: Some herbal treatments are found to have promising laboratory results, as well as in early-phase clinical trials, but the reality is that there is very little or no strong, rigorous proof in a larger number of clinical trials validating the safety and efficacy of these treatments for cancer.

Hepatotoxic and Nephrotoxic:

Some herbs can produce toxic reactions in high therapeutic doses or on prolonged use, causing damage to either the liver or kidneys. The best-known examples are Kava and Comfrey, which have been associated with acute liver toxicity [73]. Potential Carcinogenicity: Some herbs may provide components with potential cancer-promoting activity or interferers with the normal physiology of the body. [74] For instance, Pennyroyal oil is implicated in liver damage and toxicity, but in some cases, certain herbs can increase cancer risk by interacting with DNA or inciting inflammation.

Gastrointestinal Problems: Among the most common side effects for herbal products are nausea, vomiting, diarrhea, and/or a stomach ache. Ginger is an example of a common herbal medicine that is used for the treatment of nausea, where high doses may even elicit stomach upsets or diarrhea. [75].

Allergy Reactions: Some people may develop allergic reactions from herbal products, with symptoms ranging from mild rashes on the skin to serious complications such as difficulty breathing. Echinacea, for example, will bring an allergic condition to some individuals, especially to those previously sensitized to ragweed. [76]

Common Herbs Used in Cancer Treatment Turmeric: Curcumin is among the anti-inflammatory and antioxidant features that curcumin has; studies have also been conducted to see how it might prevent and treat cancers. But large doses can cause gastrointestinal upsets and may interfere with the chemotherapy drugs. [77.] Ginseng: There is specific immunomodulating effect believed to ginseng, but some researches suggest that some pediatric patients would have improvement in his or her well-being in case of using ginseng. It also interferes with blood-thinners like Warfarin. [78]. Green Tea: It is one of the antioxidants, especially the catechins which come within the green tea; they may be helpful for cancer prevention. However, it may interfere with some of the chemistry drugs and cause damage to the liver when taken in large doses. [79]. Milk Thistle: Among the benefits, perhaps, in addition to being commonly used as a liver-protectant, there is little concrete evidence to argue that it could also assist in the management of some chemotherapy side effects. Still, its administration needs to be regulated on the possibility of an interaction with chemotherapy. Astragalus: This is a very common immuno-stimulatory herb that most times is used with or for combination chemotherapy. This is quite promising but would not be safe from being found to be one of those herbs that interacts with medications, causing possible overstimulation of the immune system.

Challenges in Herbal Drug Development Cancer Treatment:

Medicinal preparations are herbal medicines whether presented singly or in combination. Traditional medicines contain the following: Medicinal materials are usually associated with all the others. Plants, minerals, etc., organic matter, etc. Preferably, herbal medicines involve those medicinal procedures or medicines by which a patient with plant-based therapeutics is healed or comforted from his ailments. [80]. Made with eco-friendly processes, renewable raw material resources will result in cost benefits; people growing these primary materials should be benefited from them. India is called the "Emporium of Medicinal Plants" because of the availability of thousands of medicinal plants grown in various bioclimatic zones. Medicinal plants are still very important in providing important healing agents in both modern and traditional medicine. The trending research area is the efficacy of plant-based pharmaceuticals in traditional medicine, thus making it economical and less side effects involved. As reported by WHO, approximately 80% of the global population still relies on herbal medicines for healthcare reasons Patients can be included based on either a diagnosis according to modern or herbal medicine. A herbal diagnosis may thus differ from a modern diagnosis, concerning the understanding of the disease and therefore the disease criteria. Setting up the definition for inclusion and exclusion criteria becomes a challenge, leading to the formation in the first place of fairly homogeneous subject groups according to herbal diagnosis. For the case set forth, Jonas and Linde have set up a “double classification method”, whereby subjects will, in the first instance, be diagnosed using modern diagnostic criteria and later classified according to the traditional system. Treatment will follow traditional classification, and outcome will be evaluated according to criteria from both systems. In herbal medicine, the outcome of treatment rests on extensive patient compliance. On the one hand, placebo effects have traditionally been utilized in all their forms, including imparting psychosocial support along with physical treatment, so as to maximize nonspecific variables that would actively contribute toward the success of any practice. The herbal medicines are complex by virtue of being mixtures of active constituents and variables regarding their administration. Hence, herbal treatment outcomes are able to proceed through the willingness and determination of the patient to undergo the treatment. However, these factors can to some extent be obviated by the application of blinding and randomization.

Future Direction and Prospect Personalized Medicine:

Personalized medicine is a medical concept that, although often regarded as the same as precision medicine, classifies patients into distinct groups on the basis of expected responses to or likely risks of infection by the disease. In this way, individualized preferences, procedures, interventions, and/or products will be brought to that specific level per patient. While the terms are, indeed, used to mean separate things, P4 medicine, PM, personalized medicine, and stratified medicine can be used as synonyms for the description of this idea. As it has been since Hippocrates, individualized, one-at-a-time treatments of all patients have even become more popular today with the advent of new diagnostic and informatics tools for understanding the molecular basis of disease, particularly in genomics. That provides us with a clear basis for grouping or stratifying linked patients. Personalized medicine is listed as one of 14 "Grand Challenges for Engineering" in an initiative spearheaded by the National Academy of Engineering (NAE), as being potentially one of the most critical and promising pathways toward truly achieving "optimal decisions about health for individuals" and thus addressing "Engineer better medicines."

These are some of the primary and main objectives of precision medicine in the case of cancer treatment:

1. To figure out the best treatment for that particular patient.
2. Avoid giving those treatments that don't work for a specific subset of patients.
3. Avoid unnecessary side effects, trauma, and risks of breast cancer surgery.
4. Determine who can benefit from any specific cancer therapy.
5. Develop targeted therapies that address specific tumor cells or cesthodal pathways.

Indeed, they produce promising exploratory results; something appears to be missing: a comprehensive external validation. The authors state that evaluating this study on five hundred and sixteen studies on the use of artificial-intelligence algorithms for diagnostics on medical images, only 31 (or 6%) validated their models in external test cohorts, data collected outside or within the same institution at a different period from the one providing the training data. Such dependence on homogeneous, single-institution, or single-scanner training data might limit the applicability of radiomics models. This shows that robust multi-institutional and multinational databanks of medical imaging are needed to design robust radiomics tools for clinical use.  This is where data sharing would help mitigate the problem of lack of different imaging data.235 These include facilities established such as "The Cancer Imaging Archive"(TCIA), which have been put in place to enable indedistanced de-identified imaging collections with clinical data and other digital infrastructure for sharing of data. As of December 2019, TCIA has nine HNSCC collections which consist of CT, MRI, and FDG-PET imaging data. It is possible to diminish imaging data inconsistencies using pre-processing techniques like resampling and filtering. But with each passing day, this appears to have smaall significance as it becomes closer to the clinical application of AI-based image analysis. Thus, standards must be created for reconstruction and acquisition parameters shared between providers and manufacturers. Further, it reduces variability in defining volumes of interest (VOI) or regions of interest (ROI) among different observers or even within the same observer through semi-automated or automated segmentation tools. There have been efforts to standardize radiomics features, especially with initiatives like "The image biomarker standardization initiative"(IBSI). The use of open-source feature libraries and radiomic extraction software packages such as "PyRadiomics"or the "Imaging Biomarker Explorer" will eventually meet also reproduce reproducible feature extraction and ease reporting of definitions for features and is gaining high adoption in newer publications.

CONCLUSION:

It is evident that the natural sources, particularly plants, should be examined for potential therapeutic agents in cancer treatment, given that almost 50% of existing medicines are derived from plants. The exploitation of drug entities from plants and other natural sources has been a long and tedious process in history. However, the modern techniques have faster processes to isolate the active constituents from the plants, making drug discovery from these plants a readily available process. The revival of herbal-based drugs, particularly in the treatment of cancer and immunologic and CNS diseases, has significant potential. Currently, about 60 herbal compounds are under study as anti-cancer medicines.  Patients most of whom had not had any very significant risk of harm through interactions with conventional medicines; risks, however, cannot yet be considered overestimated on the whole. Likewise, incidence was significantly lower compared to reports from other areas, again demonstrating how misleading extrapolation can be from one region-the UK-in one type of setting, NHS oncology-where supplement usage is often very different elsewhere. Since little is known as to whether herbal products are efficacious and safe for use, neglecting products that are frequently put into symbols of safety will allow for these areas to be improved upon if properly researched.

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