Herbal Extract Used for Colon Anticancer Activity: - A Systemic Review

The usage of plants as a cancer treatment has a lengthy history (Hartwell, 1982). More than three thousand plant species are purportedly used to treat cancer by Hartwell in his review; however, the term "cancer" is sometimes vague or referred to by other names, such as "hard swellings," abscesses, corns, warts, polyps, or tumours. In most cases, these signs would be associated with skin problems or other "tangible" or visible health issues; in rare cases, they could even be signs of cancer. However, one should approach the claims of effectiveness with caution, as cancer is likely to have a vague definition in traditional medicine and folklore. This is in contrast to other botanical remedies utilised in traditional medicine for less nebulous ailments, such pain and malaria, which tend to be more common in areas with strong traditional medicine systems. But even with these caveats, plants have been a spring of powerful anti-cancer agents, and it's noteworthy that more than 60% of anti-cancer agents used today originate from plants, marine life, or microbes in some way. Historically, people have turned to active compounds derived from plants to alleviate a wide range of health problems.  The pharmacological effects, including the anti-plasic action, are greatly affected by the secondary or naturally occurring compounds derived from plants.  Taxol, vinca alkaloids, camptothecin, podophyllotoxins, and semisynthetic or synthetic versions of these compounds are the most prominent instances of this type of cooperation.  In industrialised nations, colorectal cancer ranks third among the most common malignancies in terms of cancer-related fatalities in both sexes [1].  We now have a much better grasp of the molecular mechanisms that lead to the development of cancer and adenomatous polyps, two types of cancer.  Although the occurrence of colorectal tumours is often unpredictable, a significant portion of these cases (about 5-6%) do show a strong genetic component [1].  Aberrant promoter methylation and the activation of histone modifications are epigenetic changes that impact the genesis and progression of colon cancers.  There are promising new ways to manipulate the epigenome of cancer cells, which could lead to therapeutic benefits [2].

CARTHAMUS TINCTORIUS

Dok-Kam-Phoi, or safflower (Carthamus tinctorius L.), is a traditional medicine used to treat inflammation, gynecological issues, and cardiac conditions in several Asian and Pacific countries. Numerous active ingredients have been identified in safflower extract, including serotonin derivatives, flavonoids, kinobeone A, hydroxy safflor yellow A, erythro-alkane-6,8-diols, and tinctormine. These compounds have demonstrated a range of pharmacological properties such as bone protection, effects on lipid metabolism, antioxidant activity, anti-hypertensive effects, inhibition of proinflammatory cytokine production, anti-inflammatory effects, tumor inhibition, and inhibition of the tyrosinase enzyme. Crude dichloromethane, hexane, and methanol extracts were prepared from C. tinctorius flower collections. The cell lines utilised in the tests included BHK (baby hamster kidney), SW620 (human colon carcinoma), and Hep2 (human laryngeal carcinoma).  To test for cytotoxicity, these cell lines were grown and exposed to crude extracts of C. tinctorius for 24 hours at different doses.  A simple colorimetric test based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used to evaluate cytotoxic activity. Sw620 cells were treated with a dichloromethane fraction at concentrations of 0.15 mg/ml for 2, 6, 9, and 18 hours, and total RNA was extracted from the cells using TRI reagent® for accurate real-time measurement of Caspase gene expression.

CASSIA FISTULA L

The cold percolation method was used to obtain the extracts. After gathering the flowers, they were left to dry in the shade at room temperature before being pulverised by hand in a mill. Hexane was used to extract the powder. The filtrate was dried using a rotary evaporator operating at decreased pressure. Chloroform, ethyl acetate, methanol, and water were used to remove the plant material's remnants. Experiments are conducted using the COLO 320 DM human colon cancer cell line. The MTT test was used to find out how long the cells survived. Staining the treated cells with annexine VFITC and propidium iodide allowed researchers to study the compound's ability to cause apoptosis. At the studied concentrations and incubation times, the Rhein IC50 values in VERO cells were undetectable. In terms of cytotoxicity, compound Rhein was substantially more effective against colon cancer cell types.  At a dosage of 200 g/mL, Rhein was shown to be 80.25 percent toxic to COLO320DM cells after 72 hours of treatment. Additionally, when same cell line was treated for 24 hours at 12.5 g/mL, cell death was also observed.  Twelve hours following treatment, COLO 320DM cells exposed to Rhein at concentrations of 6.25 and 12.5 g/mL showed signs of cell death.  At a concentration of 6.25 g/mL, 2.29% of cells died during the early stage of the cell death process and 1.94% died during the late stage.  Additionally, we found that increasing the dosage of Rhein inhibited cell proliferation in our trials without causing any undesirable side effects. The anthraquinone is the isolated chemical. Anthraquinones have anti-cancer properties [16]. Alcoholic extracts of C. fistula stem bark and leaves exhibited strong antioxidant characteristics, according to Siddhuraju et al. [17]. In principle, medicinal plants' naturally occurring antioxidants might replace chemically produced anticancer drugs.[18]

HIBISCUS

Flowering Hibiscus sabdariffa was used to obtain Hibiscus sabdariffa polyphenolic extract (HPE). To summarise, 100g of dried Hi biscus sabdariffa flowers were mixed and let to incubate in 300mL of methanol. Cells of the human colon cancer DLD-1 line were procured and grown in a controlled environment with a humidifier at 37°C and 5% CO2 in DMEM enriched with 10% foetal bovine serum (FBS).   The MTT assay was used to find out how viable the cells were.   We compared treated and untreated cells to find out what proportion of cells were viable. Finally, against human CRC cell DLD-1, HPE treatment exhibits an anticancer effect comparable to that of PCA, CA, and GCG combined treatment.  We also found that HPE decreases DLD-1's metastatic potential in human CRC cells. This may be because HPE inhibits FAK-associated signalling and Akt activation, downregulates MMP-9, MMP-2, and uPA, and decreases CD44 and c-MET. Patients undergoing treatment for colorectal cancer with surgery and anti-cancer medications may benefit from HPE, according to these results.

GARLIC- Z

Officinale (ginger) was extracted using ethanol to get the crude extract. The cell lines HT 29 and HCT 116 were obtained for the purpose of conducting studies.  The cultures were supplemented with ginger extract dissolved in 0.01% DMSO after the cell lines had been incubated overnight.  In order to identify the MTT-products, the absorbance at 550 nm was measured with an ELISA reader.  Each dot represents the average of three separate studies.  To identify cell death, researchers utilised Annexin V-FITC.  The results showed that ginger extract inhibited the growth of colon cancer cells HCT 116 and HT 29, as well as triggered cell death.  The results suggest that ginger may enhance cell death through blocking the GoG1 gene. Thus, we may do additional research into ginger extract in the future to see if it may be used as an alternate chemotherapeutic treatment for colon cancer in humans.

ALOE VERA

In order to eliminate any dust or other impurities, the freshly chopped A. vera leaves were thoroughly rinsed with water and then dried using filter paper (Whatmann 41). The leaves were arranged vertically in a becher for a single night to extract the anthraquinone-rich brown latex. After halving the leaves lengthwise, scraping the gel out with a spoon, chopping the skins into small pieces, and then homogenising them with phosphate buffered saline (PBS) in a Waring blender were the next steps. Following filtration through cloth, the homogenate was centrifuged at -10°C and 10,000 rpm for 30 minutes to extract the filtrate. The transparent liquid on top was later identified as "A. vera leaf skin crude extract" after undergoing lyophylization. To screen for cytotoxic activity, the MTT colorimetric assay, originally established by Mosmann in 1983 with certain modifications, was utilised. Using the dose-response curve, we were able to determine the cytotoxic doses of the extracts that result in a 50% inhibition of cell growth (IC50). In order to determine the cytotoxic effect of A. vera extracts and controls, the IC50 values of cell lines were compared. 6) A

CORIANDER SATIVUM  

Following an air drying process and grinding using a mechanical grinder, the leaves were passed through a screen and sealed in an airtight container.  The 25 grammes of air-dried powder were subsequently refluxed with ethanol continuously at 45?C for three hours using a Soxhlet device.  In order to create a 100 mg/ml stock solution of crude ethanolic extract, the dried extracts were diluted with a 0.25% dimethyl sulphoxide (DMSO) solution.  Bioactive substances such as alkaloids, flavonoids, tannins, saponins, and cardiac glycosides were detected in an ethanolic extract of Coriandrum sativum that had been tested for phytochemicals.  Coriandrum sativum exhibited a significant level of DPPH scavenging activity, inhibiting it by 60.14 percent [Fig., 1]. The extract's FRAP readings showed that its reducing power rose as the concentration did [Fig., 2].  Using the MTT assay, we determined how well the ethanolic extracts worked on HT29 cancer cell lines.  We displayed the values of the percentage viability of treated cells versus the concentration of the extracts.  This research proved that Coriandrum Sativum's antioxidant and anticancer properties worked against HT-29 cells.  The MTT experiment demonstrated that cancer cell lines incubated with Coriandrum Sativum had a substantial decrease in cell viability and an increase in dead cells as the extract concentration was increased.  This means that the ethanolic extract of C. sativum had a cytotoxicity level of 93.8%.  Coriandrum sativum leaves, when added to a healthy diet, may thus help alleviate colon cancer symptoms.

PISTACIA ATLANTICA AND PISTACIA LENTISCUS-

CMG's traditional medicinal and culinary uses date back thousands of years in the Middle East and Mediterranean.  In vitro experiments with human colon cancer HCT116 cells demonstrated that a hexane extract of CMG (He-CMG) induced apoptosis, also known as programmed cell death.  Cancer cells treated with CMG entered apoptosis after G1 cell cycle arrest, substrate detachment, and subsequent cell cycle arrest.  The intensity and length of time that He-CMG was administered had an effect on this anoikis, which is related to detachment-induced apoptosis.  The activation of three essential apoptotic caspases—caspase-3, caspase-8 and -9—was induced by CMG.  It appears that cell detachment occurs before apoptosis induction, since caspase activation follows cell detachment. Caspases were determined to have no role in cell detachment but in apoptosis. Inducing cell death required the caspase-8 and caspase-9 pathways, which are located in the mitochondria. Over time, cells treated with He-CMG showed morphological characteristics characteristic of cell death, as observed by electron microscopy.  These findings highlight the need for more in vivo and in vitro investigations on CMG and its components to determine their anticancer potential.  It is necessary to isolate and identify the particular bioactive compound(s) in He-CMG that cause its anticancer actions.CMG represents a promising natural source for developing new anticancer agents targeting the apoptosis pathway in cancer cells.

EUGENIA JAMBOLANA (JAVA PLUM)

Researchers Venkata Charepalli et al. looked into the anti-cancer effects of extracts high in anthocyanins from fruits of the Eugenia jambolana (Java plum) tree using HCT-1116 and CSCs, which are human colon cancer cells.   There were several anthocyanins found in JPE, according to results from HPLC-MS analysis. These included delphinidin, cyanidin, petunidin, peonidin, and malvidin glucosides.    The MTT and cell counting assays showed that at doses ranging from 30 to 40 μg/mL, JPE suppressed proliferation of HCT-116 colon cancer cells by more than 60%, and this effect was dose-dependent.    Results from TUNEL assays, DNA fragmentation, and caspase 3/7 activation indicated that JPE triggered cell death in colon CSCs and HCT 116 cells.  An increase of more than 75-165% in apoptosis was seen in colon CSCs treated with 30-40 μg/mL JPE. JPE inhibited colony formation capacity and colon CSC "stemness" in a dose-dependent way, suggesting a suppression of the capacity for self-renewal. Apart from anthocyanins, JPE also included flavonols, flavanones, and stilbenes, which are other polyphenolic chemicals that may be intricate in anti-cancer properties.

PUNICA GRANATUM

One of the leading killers on a global scale is cancer.  Because of the serious adverse effects that conventional chemotherapeutic treatments might cause, scientists are looking for alternatives, such as herbal remedies.  The Punicaceae family includes the pomegranate, or Punica granatum, which contains several polyphenolic compounds with potential cancer-fighting effects.   This review explores the function and process of bioactive pomegranates in cancer treatment.  Some of the compounds found in pomegranate include ellagitannins, proanthocyanidins, flavonoids, and phenolics.  These chemicals have anti-inflammatory, anti-cancer, and antioxidant capabilities.  Polyphenols limit cancer cell growth and survival by targeting various biological pathways. They induce apoptosis, arrest the cell cycle, inhibit angiogenesis, modulate signaling pathways (NF-kB, MAPK), suppress proliferation, and inhibit metastasis and invasion. Specific mechanisms depend on the cancer type and bioactive compound. Polyphenols improve immunomodulatory properties, reduce inflammation, and regulate cytokine balance in the gut. Nanocarriers like polymeric micelles, liposomes, nanoparticles improve the bioavailability, targeted delivery, and anticancer efficacy of pomegranate polyphenols. Encapsulation protects the compounds and enables controlled release. Clinical studies on pomegranate extracts/juice in prostate, colorectal, and breast cancers indicate their potential for modulating biomarkers, minimal side effects, and anti-tumor effects. However, more extensive trials are warranted.

GRAPE

Grape is a woody, perennial vine plant that grows fruits (grapes) used to make wine, juice, jams, and other products. The entire grape plant has been utilized, including the fruits, seeds, leaves, stems, and roots. Grapes are rich in various polyphenolic compounds like resveratrol, quercetin, catechins, anthocyanins which exhibit antioxidant, anti inflammatory, anti-cancer activities. Grape Seed Extract (GSE): Rich in proanthocyanidins, shown to have anti-cancer effects against various cancers like colon, breast, prostate by inducing apoptosis and suppressing proliferation. Resveratrol and Anthocyanins: A stilbene found in grape skins, seeds, stems. Has anti-aging, cardioprotective, neuroprotective, anti-inflammatory and anti-cancer effects by modulating multiple cellular pathways.

MORINGA OLEIFERA

 Traditional medicine has long recognised the medicinal value of the moringa oleifera (MO) plant for a variety of ailments, including cancer.  Examining the potential anti-cancer effects of MO extracts from leaves, bark, and seeds on MDA-MB-231 and HCT-8 cancer cell lines was the main goal of the research.   Parts of MO plants grown in Saudi Arabia, such as leaves, bark, and seeds, were extracted using an ethanol solvent.   Researchers employed gas chromatography mass spectrometry (GC-MS) to identify the compounds included in the extracts.   Tests for cell migration, cell cycle progression, cell death, cell viability, and colony formation were administered to the HCT-8 and MDA-MB-231 cell lines.   According to GC-MS analysis, the bark and leaf extracts included a number of compounds with demonstrated anti-cancer capabilities, including eugenol, isopropyl isothiocyanate, D-allose, and hexadecanoic acid.   The ability of both cancer cell types to survive, move about, and form colonies was significantly reduced by bark and leaf extracts.   Bark and leaf extracts significantly increased cancer cell apoptosis (up to sevenfold compared to control).   Bark and leaf extracts quadrupled the rate of cell cycle arrest, namely in the G2/M phase. There was no evidence that seed extracts had any anti-cancer properties.  Because of the bioactive anti-cancer chemicals found in Moringa oleifera, preparations from the plant's leaves and bark showed strong anti-cancer action against cells from colorectal and breast cancers.  Results from this study point to the possibility of developing novel medications derived from Moringa plant extracts grown in Saudi Arabia as a means of treating colorectal and breast cancer.

ROSA CANINA

Using Rosa canina extracts to Fight Caco-2 Human Colon Cancer: An Antiproliferative and Antioxidant Study The research looked at how various parts of Rosa canina (rosehip) extracts affected colon cancer in humans.  The Caco-2 cell lineage Protective Agent Material substances:  There was 101 milligrammes per kilogramme of ascorbic acid in the vitamin C component of the fruit.  The neutral polyphenol fraction had a dry weight of 40.8 mg, with catechin and rutin being the most prevalent.  Gallic acid was the most prevalent of the acidic polyphenol fraction's 960 μg/kg dry weight.  Both the low and high doses of the extract fractions exhibited considerable cytotoxicity against Caco-2 cells after 72 hours.  The process of cell death.  All fractions caused Caco-2 cells to undergo apoptosis, according to flow cytometry analysis.  With a concentration of 125 mg/L, fractions 2 and 1 caused early cell death, but fractions 3 and 4 caused late cell death.  Fragrances 1 and 2 caused cell cycle effects of late apoptosis at 1000 mg/L.  At 125 mg/L, fractions 1 and 2 showed a rise in S phase, which means the cell cycle stopped in S phase.   Fractions 3 and 4 saw an increase in the G2 phase and a decrease in the S phase at 125 mg/L.   At a concentration of 1000 mg/L, all fractions disrupted the normal course of the cell cycle.   Why Antioxidants Are Important:   In Caco-2 cells treated with hydrogen peroxide, ROS generation was markedly reduced by all fractions.

CURCUMIN

Curcumin, an ingredient in turmeric, has shown anti-cancer effects in several cancer cell lines and pre-clinical animal models.  The development of curcumin as a cancer chemopreventive and chemotherapeutic drug has showed encouraging results in multiple clinical trials involving patients with colorectal cancer.   Curcumin influences signalling pathways such JNK, NF-κB, AP-1, Egr 1, COX-2, and iNOS to induce cell death and cell cycle arrest. Through downregulating matrix metalloproteinases, it blocks cell signalling linked to angiogenesis, metastasis, and migration. Curcumin modulates carcinogen metabolism by interacting with aryl hydrocarbon receptor (AhR) and UDP-glucuronosyltransferases. Curcumin has low bioavailability due to rapid metabolism and elimination.Strategies like combining with piperine, liposomal formulations, and nanoparticles have improved bioavailability in animal studies. Five phase I clinical trials in colorectal cancer patients established the safety of curcumin up to 8g/day doses.Some trials showed potential chemopreventive effects like reduced M1G levels and downregulation of COX-2 in colorectal tissue at higher doses.More studies are needed to evaluate efficacy, optimal dosing, and potential interactions with chemotherapy drugs metabolized by glucuronidation. Curcumin is a promising compound for colon cancer chemoprevention targeting multiple pathways based on preclinical evidence.Overcoming bioavailability issues and further clinical testing are needed to establish its preventive/therapeutic utility.

ECLIPTA ALBA

Existing treatments like surgery and chemotherapy have limitations and toxicity issues, so there is a need for new therapeutics from natural sources like medicinal plants. Eclipta alba (L.) is an herb used in Ayurveda that contains compounds like wedelolactone, β-sitosterol with potential anticancer activity. A complete Eclipta alba plant was extracted with methanol. We treated normal WI-38 cells with the extract and a number of cancer cell lines (HCT-116 colon, PC-3 prostate, MCF-7 breast, RCC-45 renal). The clonogenic and migratory assays assessed anticancer properties, while the MTT assay investigated cytotoxicity.  As compared to other cancer cell lines, Eclipta alba extract exhibited substantial and selective cytotoxicity against HCT-116 colon cancer cells. To normal WI-38 cells, it was quite poisonous. There was a dose-dependent inhibition of HCT-116 cell migration and colony formation by the extract. This study presents the first evidence that an extract from Eclipta alba has the ability to selectively kill colon cancer cells while having minimal effect on healthy cells. The extract inhibited key properties like colony formation and migration required for colon cancer growth and metastasis.This suggests Eclipta alba extract contains promising compounds that could be developed into novel colon cancer therapeutics in the future.