ANTI-CANCEROUS ACTIVITY OF MEDICINAL PLANTS

ANTI-CANCEROUS ACTIVITY OF MEDICINAL PLANTS

Saddam *, Suman and Shashi Alok

Institute of Pharmacy, Bundelkhand University, Jhansi, Uttar Pradesh, India.

ABSTRACT: The rising burden of cancer worldwide calls for an indispensable treatment result. Herbal drug provides a veritably doable volition to western drug against cancer. This composition reviews the named plant species with active phytochemicals, the animal models used for these studies, and their nonsupervisory aspects. This study is grounded on a scrupulous literature review conducted through the hunt of applicable keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty shops were named grounded on defined selection criteria for their potent anticancer composites. The detailed analysis of the exploration studies revealed that plants play a necessary part in fighting different cancers similar as bone, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in-vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis- converting enzymes by the secondary metabolites in the plant excerpts. Studies that reported in-vivo conditioning of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring further plants, their active composites, and the medium of anticancer conduct for use as standard herbal drug.

Keywords: Cancer, Apoptosis, Herbs, Cell lines, In-vivo

INTRODUCTION: The burden of cancer rose to 18.1 million new cases and 9.6 million deaths in 2018. With 36 different types, cancer mainly affects men in the form of colorectal, liver, lung, prostate, and stomach cancer and women in the form of breast, cervix, colorectal, lung, and thyroid cancer ¹. Treating cancer has come a whole new area of exploration. There are conventional as well as truly modern ways applied against cancers. A variety of ways i.e., chemotherapy, radiation remedy, or surgery are used for treating cancer. Still, all of them have some disadvantages ². The use of conventional chemicals bears side goods and venom ³.

But as the problem persists, new approaches are demanded for the control of conditions, especially, because of the failure of conventional chemotherapeutic approaches. Therefore, there is a need for new strategies for the prevention and cure of cancer to control the death rate because of this complaint. In recent times there has been a raised trend in the use of medicinal shops in the developing countries because of their safety and lower adverse effect especially when compared with synthetic conventional drugs.

Sources and Methodology: The most applicable literature was recaptured through a scrupulous search on the electronic databases, Web of Science, Scopus, PubMed, and Google Scholar. The keywords and expressions used during the search were Medicinal plants, Anticancer exertion, Anticancer sauces, Anticancer plants, Medium of action, Animal models, in-vitro exertion, and in-vivo exertion.

The number of applicable papers perfected after extraction and analysis through the combination of the below keywords expressions and the addition criteria was 200. The addition was grounded on two sets of criteria.

1. According to the first set, i.e., general criteria, papers named for this handwriting had Reported the traditional anticancer exertion of plants and their corridor.
2. Reported the anticancer part of excerpt or pure composites from plants.

The alternate set of criteria was used for opting specific anticancer plants whose phytochemicals are bandied in detail. For this purpose, twenty plants were named for which recent papers were available that

1. Studied in-vitro and in-vivo anticancer conditioning of herbal products.
2. Reported the anticancer/ antitumor exertion of active composites from the plants.
3. Assessed the in-vivo anticancer exertion of the herbal anticancer products.

Activity of Plants against Several Types of Cancers:

FIG. 1: ILLUSTRATION OF ACTIVITY OF PLANTS AGAINST SEVERAL TYPES OF CANCERS. The icons were taken from Bio-render illustrator ⁴

Medicinal Plants and Cancer: The anticancer parcels of plants have been recognized for centuries. Sequestration of podophyllotoxin and several other mixes (known as lignans) from the common May apple (Podophyllum peltatum) ultimately led to the development of drugs used to treat testicular and small cell lung cancer. Till now( National Cancer Institute) NCI had excavated further than, 35000 plant species which reacted in the discovery of anticancer drugs analogous as Vincristine, Vinblastine, Taxol, Etoposide analogs, Indicine – N- oxide, Camptothecin and analogs and multitudinous others. With the knowledge of available traditional medicine, a new approach could be espoused which combine some or all of below methods ⁵. Paclitaxel (Taxol TM) was originally isolated from Taxus brevifolia used in treatment of ovarian and bone cancers which was assumed to bind the tubulin subunit of microtubules and stabilizes the microtubule to normal disassembly ^5-6. Sauces these days are also being used as chemo- protectant against cytotoxicity that are caused by anticancer drugs. NCI has been honored, 3000 plant species have demonstrated reproducible anticancer exertion (data available at http//www.ars-grin.gov/duke/ Since, plants are a rich source of natural composites that are characterized by their remedial goods, studying these composites is allowed to be a promising line for exploration on cancer ^6-7. In this environment, phytochemicals, secondary metabolites uprooted from shops, have different operations, including antidiabetic, anti-inflammatory, cardiovascular defensive, antioxidant, and anticancer effects ⁷. In particular, these phytochemicals can be classified into different groups similar as flavonoids, alkaloids, phytosterols, terpenoids, sulfides, polyphenols, and others, which have been considered an important force for new anticancer agents ^8-9. Hence, factory secondary metabolites are honored with numerous properties similar as tumor growth inhibition, apoptosis induction, vulnerable modulation, and angiogenesis suppression ¹⁰. As well, several epidemiological studies have reported the role of phytochemicals and their deduced analogues in modulating tumor cell- cranking proteins, enzymes, and signaling pathways, stimulating DNA form mechanisms, and conquering free radicals product ^{11, 12}.

They also interact with numerous intracellular pathways that regulate cell growth, similar as the STAT3, PI3K/ Akt/ NF- κB signaling pathway, mTOR, and the Bcl- 2/ Bax mitochondrial pathway ^{9, 13, 14, 15} So, this present review aimed at exploring the implicit anticancer composites from the medicinal plants and we've tried to choose the most effective and well- known phytochemicals that display a distinctive anticancer activity. As well, we described these phytochemicals completely, starting with their chemical structure and ending with their antitumor exertion.

Plant Compounds with Anticancer Properties: Composites which have been linked and uprooted from terrestrial plants for their anticancer properties include Polyphenols, Brassinosteroids and Taxol’s.

1. Polyphenols
2. Flavonoids
3. Brassinosteroids
4. Anticancer plant-derived drugs enhancing drug administration.

Polyphenols: Polyphenols are allowed to have apoptosis converting properties showing anticancer properties which can be employed. The mechanism in which polyphenols are allowed to carry out apoptosis inauguration is through regulating the rallying of bobby ions which are bound to chromatin converting DNA fragmentation. In the presence of Cu (II), resveratrol was seen to be able of DNA declination ¹⁶.

Example: curcumin treated cancer cells in various cells lines have shown suppression of the Tumour Necrosis Factor (TNF) expression through interaction with various stimuli ¹⁷.

Flavonoids: Flavonoids set up to demonstrate cytotoxicity on cancer cells and to have high free revolutionary scavenging activity ¹⁸. Flavonoids inhibit the expression of NF- κB which is demanded for cancer cell survival and angiogenesis and proliferation Purified flavonoids have also shown anticancer conditioning against other mortal cancers including; hepatoma( Hep- G2), cervical carcinoma( Hela) and breast cancer( MCF- 7) ¹⁹. The flavonoids uprooted from Erythrina suberosa stem bark (4 ’- Methoxy licoflavanone (MLF) and Alpinumi so flavones (AIF)) were shown to have cytotoxic effects in HL- 60 cells (mortal leukemia) ²⁰.

Brassinosteroids: Brassinosteroids have been used in examinations to treat a range of cancer cell lines which include; T- lymphoblastic leukemia CEM, multiple myeloma RPMI 8226, cervical carcinoma HeLa, lung carcinomaA-549 and osteosarcoma HOS cell lines (21). Also included are cell lines in breast cancer and prostate cancer. Estrogen receptor (ER), epidermal growth factor receptor (EGFR) and mortal EGFR- 2 (HER- 2) are some of the critical proteins which are targeted in treatment of breast cancer as they're abundant in breast cancer cells similar as MCF- 7, MDA- MB- 468, T47D and MDA- MB- 231. Brassinosteroids will interact or bind to receptors of these proteins and inhibit the growth of both hormone sensitive and hormone asleep cancer cells ^22-23. Also, Brassinosteroids overlook induce cell cycle blockage

Anticancer Plant-Derived Drug:

Plant: Deduced drugs are asked for anticancer treatment as they're natural and readily available. They can be readily administered orally as part of case’s salutary input ^24-25.

There are exceptions similar as cyanogenetic glycosides, lectins, saponins, lignans, lectins and some taxanes ^26-27. Still, arenon-toxic to normal cell lines and show cytotoxicity in cancer cell lines, these medicines can be lead into clinical trials for further, if plant- induced drugs can demonstrate selectivity in exploration. herapeutic development. Plant- induced drugs can fall under four classes of drugs with the following conditioning; methytransferase impediments, DNA damage preventative medicines or antioxidants, histone deacetylases (HDAC) impediments and mitotic disruptors. Composites including sulforaphane, isothiocyanates, isoflavones and pomiferin are considered to be HDAC inhibitors. They inhibit the activity of carcinogenic proteins.

For Example: Sulforaphane has shown to inhibit important targets in breast cancer proliferation. Decreased expression of ER, EGFR and HER-2 resulted from HDAC inhibition by sulforaphane treatment in breast cancer cell lines ²⁸. Derivations of vinca alkaloids, vincristine, vinblastine, vinorelbine, vindesine and vinflunine are medicines which will inhibit the dynamics of microtubules by binding to β- tubulin. Taxanes similar as paclitaxel and its analogue docetaxel are also microtubule disruptors. These composites inhibit cell cycle phase transitions from metaphase to anaphase causing cell cycle arrest and apoptosis. Replication of cancer cells is reduced by paclitaxel as it stabilizes or polymerizes microtubules in the cells ^29-31. Paclitaxel was one of the first medicines to have a huge impact on cancer treatment and vincristine and vinblastine were two of the original medicines to be insulated.

Enhancing Drug Administration: With advancements and discoveries in naturally derived drugs new technologies are arising for the operation and lozenge of these anticancer composites. Administration of new medicines needs to be effective for the compound to be a successful alternative to current treatments similar as chemotherapy. Through the field of nanotechnology the use of nanoparticles (NPs), as a delivery system for drugs to reach target spots, is developing. Some composites that have demonstrated anticancer conditioning may be limited in their clinical development due to the need for high tablets. Bromelain, insulated from Aanas comosus was shown to be more effective as an anticancer agent in expression with NPs than free bromelain ^32-33.

Mechanism on Cancer Therapy:

FIG. 2: MECHANISM ON CANCER THERAPY

Advantages of Herbal Drugs over Conventional Drugs:

• Common reasons for use of herbal medicines include.
• Health promotion.
• Disease prevention.
• Increasing costs of conventional cancer treatments.
• Lack of effective drugs to cure solid tumors encouraged.
• Less side effect comparison to conventional.
• Herbal formulation have cheapness comparison to conventional therapy.
• Poor outcomes.
• Limited treatment options for a serious illness.
• Exhaustion of conventional therapies.
• Dissatisfaction with, or inefficacious conventional therapies.
• Fatal side effects or risks associated with conventional medicine.
• Belief that herbal and natural products are better or safer.
• Preference for personal involvement in the decision making process.
• Cultural or spiritual preference.

Whereas side effects of allopathic medications vary wildly from mild to severe and there are many. These may include ³⁴.

TABLE 1:

Selected Plants and Their Anticancer Activity: Some of these plants and their composites prove to be veritably effective against one or further types of cancers. Grounded on their conditioning, the following plants are named for the in-vitro and in-vivo anticancer conditioning of their composites. The rest of the important plants shortlisted for their activities are presented in Table 2 along with their activities.

1. Artemisia annua
2. Coptis chinensis
3. Curcuma longa
4. Fagonia indica
5. Garcinia oblongifolia
6. Garcinia indica
7. Hedyotis diffusa
8. Loranthus parasiticus and Scurrulus parasitica
9. Morus alba
10. Paris polyphylla
11. Perilla frutescens
12. Platycodon grandifloras
13. Prunus armeniaca
14. Rabdosiae rubescens
15. Scutellaria baicalensis
16. Scutellaria barbata
17. Tripterygium wilfordii
18. Tussilago farfara
19. Wedelia chinensis

Artemisia annua: The genus Artemisia, wide in Europe, Asia, North America, and South Africa has roughly 400 species worldwide ³⁴. Plants of the genus were used for centuries in classical drug ³⁵. Artemisia annua is a periodic short- day plant that belongs to family Asteraceae, having a brownish rigid stem. A. annua is known as sweet wormwood (Chinese q ¯ ınghao) and dona in ¯ the Urdu language in India and Pakistan ³⁶. Artimisia annua also synthesize scopoletin and 1, 8- cineole composites. Also, semi-synthetic derivations of artemisinin are also generated similar as art ether, artemether, and artesunate. Artesunate has been studied to be a veritably effective anticancer compound ³⁷. Studied the effect of artesunate. On 55 different cancer cell lines including leukemia, melanoma, lung cancer, colon cancer, renal cancer, ovarian cancer, and excrescences of the central nervous system. They suggested that artesunate was most effective against leukemia and colon cancers. Stem and leaves A. annua were subject to extraction with the help of 80 ethanol and water. Several quantitative phenolic compounds from A. annua were linked using high- performance liquid chromatography (HPLC). The extracts were tested against HeLa and AGS cell lines. The cell growth inhibition activity of stem extracts was lower compared to splint extracts. The ethanolic extracts of leaves lead to growth inhibitions (57.24 and 67.07) in HeLa and AGS cells, independently at a attention of 500 mg/ mL. HPLC analysis showed that the quantum of phenolic acids was lower in stem extract than in leaves extract of A. annua. It was concluded from the data that the antioxidant and anticancer capacity was the result of phenolic composites as well as unidentified composites within A. annua ³⁸.

Coptis Chinensis: C. chinensis extract has wide use in the treatment of cholera, dysentery, diabetes, and blood and lung cancer because of its strong antibacterial activity ³⁹. Coptis genus contains the most important and active components, similar as an alkaloid i.e., berberine Fig. 1. Berberines alkaloids are used constantly as criteria in the quality control of Rhizoma cupids (Huang Lian) products and lead to the apoptosis of mortal leukemia HL- 60 cells by down regulating nucleophosmin/ B23 and telomerase activity.

Curcuma longa: Curcuma longa (Turmeric) belongs to the ginger family Zingiberaceae. It's a rhizomatous herbaceous imperishable plant ⁴⁰. It's naturally set up in Southeast Asia and the Indian key. These plants are annually collected for their rhizomes and are also propagated from some of those rhizomes ⁴¹. C. longa possesses a broad range of pharmacological conditioning including anti- HIC (mortal immunodeficiency virus), anti-inflammatory, antioxidant goods, nematocidal and anti-bacterial conditioning. Curcumin, the main element of. Longa, plays an important part in the remedial conditioning of. Longa ⁴². Curcumin shows anticancer andanti-inflammatory conditioning as reported by numerous different studies. Cyclooxygenase (COX) - 2 plays a vital part in the conformation of colon cancer. In a study conducted by Goel et al. ⁴³, the HT- 29 colon cancer cells of humans were treated with different attention of curcumin to study the effect of curcumin on the expression of COX- 2.

Fagonia indica: Fagonia indica, locally known as “dhamasa” is a flowering plant and belongs to the family of caltrop, Zygophyllaceous ⁴⁴. Members of Fagonia rubric are known for their use as traditional drug and are set up effective in the treatment of numerous skin problems ⁴⁴. Traditionally, it was also used as a drug for curing cancer as well as ailments performing from venoms. Amino acids and proteins ⁴⁵, flavonoids ⁴⁶, alkaloids ⁴⁷, saponins ^48, and terpenoid ⁴⁹ are the phytochemicals set up in the Fagonia species. F. indica is set up to have liver defensive ⁵⁰ and antioxidant properties as well ⁵¹. The waterless extracts of F. indica have been set up veritably effective against different types of cancer specifically breast cancers. For case, Waheed et al. ⁵² Performed bioactivity- guided fractionation to insulate the active and potent bit of the F. indica extract. The activity was assessed against three cancer cell lines MCF- 7 estrogen-dependent breast cancer, MDA- MB- 468 estrogen-independent breast cancer, and Caco- 2 colon cancer cells.

Garcinia oblongifolia: Garcinia oblongifolia (Lingnan Garcinia) belongs to the family of Clusiaceae and has a wide range of pharmaceutical conditioning. The important metabolites of the G. oblongifolia species; polyisoprenylated benzophenones and xanthones have anticancer, antioxidant, antifungal, apoptotic, and anti-pathogenic properties ⁵⁴. In-vitro study showed that the bark of G. oblongifolia contains important secondary metabolites including oblongifolin A – G, oblongixanthones A – C along with other important composites. These metabolites showed maximum apoptotic conditioning in HeLa- C3 cell lines and cytotoxic properties in the cervical cancer cells ^{47, 48}. Li et al. ⁵⁵ Insulated about 40 different composites from fruit, leaves, branches, and other corridor of G. oblongifolia. They noted veritably high cytotoxic conditioning of these metabolites in the tested MCF- 7 breast cancer cell line.

Garcinia indica: Garcinia indica, generally known as kokum, is also an important medicinal plant that belongs to the Garcinia genus. The garcinol of G. indica shows positive activities in the experimental HT-29 and HCT-116.

Colon cancer cells along with normal eternalized intestinal cells (IEC- 6 and INT- 407). In another study, the fruit extract of G. indica was used for the isolation of garcinol.

Hedyotis diffusa: This herb entered significance for having antitumor properties and showed effective results in treating cancers of the liver, colon, lungs, brain, and pancreas ⁵⁶. H. diffusa contains important bioactive derivations of polysaccharides, triterpenes, and anthraquinones ^{57, 58}. Methyl anthraquinones are, one of the bioactive composites in H. diffusa, is responsible for apoptosis of numerous cancers. It shows apoptosis and inhibitory effect on the mcf- 7 cell line of breast cancer via activation of the caspase- 4/ ca2/ calpain pathway when applied in an attention of 18.62 µm for 24 h. It was observed that the s phase of the cell cycle and the chance of the apoptotic cells were markedly increased when methyl anthraquinone was applied to mcf- 7 cells ⁵⁹.

Loranthus parasiticus and Scurrulus parasitica: Loranthus parasiticus, also known as sang Ji Sheng (in Chinese), is a member of the Loranthaceae family and is extensively distributed in the South-western regions of China. L. parasiticus is a semi parasitic plant, historically used as traditional folk drug in China and Japan ⁶⁰. L. parasiticus has shown positive activity against ovarian cancer cell lines; SKOV3, CAOV3, and OVCAR- 3 ⁶¹.

Morus alba: M. alba, generally called white mulberry, is native to China, Japan, and India and is cultivated throughout the world where silkworm is raised. Their leaves are the main source of food for silkworms. Extracts from M. alba are traditionally used to cure cough, edema, wakefulness, bronchitis, asthma, nose bleeding, wound mending, eye infections, and diabetes ⁶². M. alba contains numerous pharmaceutically important composites like kuwanol, hydroxymoricin, moranoline, morusin, calystegin, albafuran, and albanol. The leaves of M. alba contain some active composites similar as quercetin, rutin, apigenin, 1- deoxynojirimycin ⁶². A study by Chon et al. ⁶³. On methanolic extract ofM. Alba leaves showedanti-proliferative goods on different mortal cell lines like pulmonary melanoma (Calu- 6), colon carcinoma (HCT- 116) and breast adenocarcinoma (MCF- 7).

Paris polyphylla: Paris polyphylla (called “Love Apple”) belongs to family Liliaceae and contains 24 species throughout the world ⁶⁴. P. polyphylla is substantially used by Indian and Chinese traditional drug system for having implicit anticancer properties. P. polyphylla consists of important secondary metabolites similar as polyphyllin D, formosanin C, β- ecdysterone, dioscin, daucosterol heptasaccharide, oligosaccharides, octasaccharide, protogracillin, trigofoenoside A, yunnanosides G- J, padelaoside B, pinnatasterone, and other saponins ⁶⁵. Steroidal saponins are the main active components because of its structural diversity andbio-activities similar as antitumor, vulnerable- stimulator, analgesic, and hemostatic parcels ^66-71. Waterless and ethanol extracts of P. polyphylla showed implicit antitumor activity against mortal liver carcinoma (HepG2 and SMMC- 7721) cell line, mortal gastric (BGC- 823) cell line, mortal colon adenocarcinoma (LoVo and SW- 116) cell line, and mortal esophagus adenocarcinoma (CaEs- 17) cell lines.

Perilla frutescences: Perilla frutescence, generally called perilla or Korean perilla or Beefsteak plant, is extensively distributed in Vietnam, China, Japan, and utmost Asian regions belong to the Labiatae family ^72-73. Economically, one of the most significant crops, civilization of P. frutescence in China and some other Asian countries is further than 2000 times old ^74-75. Stem, seed, and splint corridor of P. frutescence have been used to treat poisoning, cold, bloating, and headache ⁷⁵. Multiple in-vivo and in-vitro studies have been conducted to estimate the anticancer and antitumor eventuality of P. frutescence. Leaf extract of P. frutescence showed the loftiest anticancer activity in HepG2 cells through cell proliferation inhibition and up regulation of apoptosis- related gene expression ⁷⁶.

Platycodon grandifloras: Platy codon grandifloras, generally known as balloon flower, or Chinese bellflower, belongs to the family Campanulaceae, which is distributed through Northeast Asia. The rhizomes of P. grandifloras are veritably effective and are used as a traditional drug in China, North Korea, and Japan for treatment of different conditions like cough, sore throat, numbness, and other affections ⁷⁷. P. grandifloras contains numerous biologically active composites which include saponins, flavonoids, anthocyanins, phenolic, and polysaccharide. These composites have significant vulnerable- stimulatory ⁷⁸, anti-inflammatory ⁷⁹, hepatoprotective ⁸⁰, and antitumor conditioning. The antitumor exertion of P. grandifloras was shown in a cure- dependent manner by reducing PKC improvement of matrix metallopeptidases (MmP- 9 and MmP- 2), which caused the death of HT- 80 cells ⁸¹. Yu and Kim ⁸² insulated platycodin D from the root of P. grandiflorus and treated MCF- 7 cells with a attention of 5 – 100 µM which reduce cell viability and proliferation in a cure-dependent and time-dependent manner as compared with controlled cells. Platycodin D is a triterpene saponin insulated from the roots of P. grandiflorus shows cytotoxic effects on the mortal leukemia cells. It inhibited telomerase activity and showed a cytotoxic effect in a cure-dependent manner with an attention of 10 – 20 µM. This was shown to be achieved through down regulating the expression of mortal telomerase rear transcriptase (hTERT) ⁸³.

Prunus armeniaca: Prunus armeniaca (Armenian plum) belongs to an important plant family Rosacea. Colorful parts of the plant are used as the major source of some important antioxidant substances and are generally used against cancer and some other cardiovascular conditions ⁸⁴. The fruit part of P. armeniaca contains colorful important secondary metabolites like β- carotene, flavonoids, organic acids, thiamine, minerals, and oils ⁸⁵. The seeds of P. armeniaca contains plenty of cyanogenic glycosides, used against different types of cancers ⁸⁶. Amygdalin is one of the important glycosides of P. armeniaca, used for the treatment of prostate cancer ⁸⁷. Gomaa ⁸⁸ reported the antioxidant and anticancer conditioning of P. armeniaca at different combinations of methanolic and ethanoic extracts with water.

Rabdosiae rubescens: Rabdosiae rubescens (Chinese Dong Ling Cao) is a Chinese medicinal herb that belongs to the family Lamiaceae. It possesses multiple natural activities like antibacterial, anti-inflammatory, anti-parasitic, and anticancer ⁸⁹. R. rubescens contain important chemical compounds including monoterpenes, sesquiterpene, diterpene, and terpenoids. Oridonin, a tetracyclic terpenoid, is the main active compound in R. rubescens ⁹⁰. Oridonin gained its attention because of the remarkable properties of growth inhibition and the induction of apoptosis in cancer cells. In-vitro and in-vivo studies showed the induction of apoptosis in a variety of cancer cells by oridonin as in hepatocellular carcinoma, breast, gastric, skin, and colorectal, gallbladder, and pancreatic cancers ⁹¹.

Scutellaria baicalensis: Scutellaria baicalensis is one of the important medicinal plants species of family Lamiaceae. It's generally known as Baikal skullcap or Chinese skullcap and is set up in different regions of the world including East Asia, Europe, and the Russian Federation. Its root part is known as Scutellariae radix and used as traditional Chinese drug for the treatment of hepatitis, respiratory, and gastrointestinal diseases ⁹². The root parts have maximum flavonoid content having multiple pharmacological properties ⁹³. About 60 different flavonoids have been linked in S. baicalensis which showed maximum antioxidant activities ⁹⁴. The four flavones metabolites also showed antimutagenic properties ⁹⁵. Wo´zniak et al. ⁹⁶. Studied the antioxidant capabilities of four flavones baicalein, baicalin, wogonin, and their glucuronides compounds and wogonoside. These flavones have different antioxidant capacity depending on the chemical structure and mechanisms of activity.

Scutellaria barbata: Scutellaria barbata, the acerbic skullcap is a crucial medicinal plant species of family Lamiaceae, used to treat seditious and cancer diseases ⁹⁷. It's rich in important secondary metabolites like alkaloids, flavones, steroids, and polysaccharides ⁹⁸. In-vitro studies showed positive activities against a vast range of cancers i.e., colon cancer, lung cancer, hepatoma, and skin cancer ⁹⁹. The apigenin and luteolin insulated fromS. barbata gave cytotoxic activity against both mortal breast cancer cell line MDA- MB- 231 andnon-transformed breast cell line( MCF10A) ¹⁰⁰. Also, scutellarein was set up to retain stronganti-breast cancer activity demonstrated in MDA- MB- 468 cell lines ¹⁰¹. Scutellarein increased the attention of mitochondrial superoxide and peroxide while dwindling the position of glycolysis, braking the growth of cancer cells by lowering ATP synthesis.

Tripterygium wilfordii: Tripterygium wilfordii of the family Celastraceae is also known as “ Thunder God Vine, ” and is native to Korea, China, and Japan. It's generally used for the treatment of multiple conditions similar as rheumatoid arthritis, systemic lupus erythematosus, nephritis, asthma, and cancers ¹⁰². T. wilfordii produces important bioactive emulsion triptolide which is used as an immunosuppressive and anti-proliferative agent ¹⁰³. It has a five- membered unsaturated lactone ring and is used against different bone cancer cells by activation of pro-apoptotic composites by modulating several signaling pathways ^104-105. In-vitro studies showed anti- proliferative and pro-apoptotic conditioning against excrescence cell lines ^106-108. He et al. The overall results showed that anticancer parcels of tri ptolide are directly identified with the blockage of two endothelial receptor- intermediated signaling pathways. Triptolide showed more negative conditioning against the proliferation of HUVECs as compared to normal cells like skin keratinocytes HaCaT cells and other liver cells L- 02 ^109-110.

Tussilago farfara: Tussilago farfara (generally called coltsfoot) is one of the important medicinal shops, grown in Europe and colorful regions of western and central Asia, generally used against cancer. It possesses a high volume of flavonoids and other phenolic composites and some trace rudiments (Zn, Mg, and Se). The presence of these substances plays a crucial part in the anticancer conditioning of this factory. Maximum scavenging exertion was recorded in water excerpt as compared to ethanol excerpt. It shows a 20.9 antioxidant exertion. Further, this factory showed maximum antioxidant exertion both using DPPH and incentive model ¹¹¹. The quercetin- glycosides insulated from the flower cub of T. farfara shows the loftiest antioxidant exertion ¹¹². Lee et al. ¹¹³ reported the (TF) - convinced cytotoxic and apoptotic conditioning of the flower part ofT. farfara in mortal colon cancer cell line( HT- 29) by using a methanolic excerpt. Fatykhova et al. ¹¹⁴ showed the genotoxic exertion of T. farfara condiment juice against known genotoxic composites like nalidixic acid in SOS chromotest and furacilin in Rec assay. Their findings showed that dilution of the condiment juice gave maximum antimutagenic porperty in SOS chromotest as compared to furacilin in Rec assay.

Wedelia chinensis: Wedelia chinensis (Chinese Peng qi ju), indigenous to India, South- East Asia, and China, is one of the important anticancer plants belonging to family Asteraceae which is rich in numerous important secondary metabolites like phenol, flavonoids, and tannin ¹¹⁵. The essential oils of W. chinens is give a positive effect on lung cancer during the in-vitro study. The GC- MS analysis recorded the presence of two important compounds carvacrol and trans- caryophyllene. Highanti-scavenging activities were set up at different levels of dose.

The study of B16F- 10 carcinoma metastatic cell line showed that the attention of some important antioxidant enzymes (including catalase, superoxide dismutase, and glutathione peroxidase) increased numerous crowds in the treatment groups. Also, the amount of glutathione also increased while the concentrations of other compounds similar as lipid peroxidation and nitric oxide were dropped. The histopathology studies further vindicated that these essential oils show negative effects on cancer development ¹¹⁶.

In-vivo Studies of Anticancer Herbal Medicine: an Overview: The herbal drugs are tested both in-vitro and in-vivo. The anticancer conditioning of the colorful medicinal plants have been tested in vivo using different animal models Fig. 3. There are numerous studies available on in-vivo experiments of the numerous different anticancer shops in mice models. For instance, dihydroartemisinin was reported to inhibit excrescence tissue, increase the position of interferon- gamma (IFN- γ), and decrease interleukin 4 (IL- 4) in excrescence- bearing mice ¹¹⁷. also, artesunate, a outgrowth of artemisinin is also reported to be a promising medicine against angiogenic Kaposi0 s sarcoma ¹¹⁸, growth inhibition of A549 and H1299 lung excrescences by 100 mg/ kg cure ¹¹⁹, the repression of mortal prostate cancer xenograft ¹⁵⁷ and the inhibition of leukemia growth in mice ¹²⁰. Irradiation of C57BL/ 6 mice combined with a cure of 2 mg/ kg doubly a week was proved effective against lung carcinoma ¹²¹. The effectiveness of berberine was enhanced when it was used in combination with other agents. Coptisine, another alkaloid of Coptidis rhizoma is proved to have anticancer goods when used in attention of 150 mg/ kg against BALB/ c raw mice by suppressing excrescence growth and reducing cancer metastasis. The inhibition of the RAS- ERK pathway was suggested as the medium for this exertion ¹²². Another study was also performed on the raw mice on the HepG2 cells by applying the waterless excerpt of H. diffusa which inhibits proliferation of cells in a dose-dependent manner, also detention S phase and arrest cells in G0/ G1 phase ¹²³.

FIG. 3: A DEPICTION OF GENERAL STRATEGIES APPLIED FOR ASSAYING EXTRACTS/ PHYTOCHEMICALS FROM IMPORTANT MEDICINAL PLANTS FOR THEIR ANTICANCER ACTIVITY BOTH IN-VITRO AND IN-VIVO

Regulatory Aspects of Herbal Anticancer Drugs: It's generally established that the medicines including the anticancer composites bear phase III clinical exploration trials for marketing warrants. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines require at least one controlled trial in Phase III with statistically significant results for the green signal to market them ¹²⁴. Except for exceptional circumstances, all the medicines need to go through all the phases of trials according to the guidelines of transnational agencies similar as the FDA and EMA. Still, it has been observed that pharmaceutical companies diverge from the standard protocol and start testing new compounds on mortal subjects before than the defined timeline. The reason for similar practices is to accelerate the approval of these composites under the pressure of investors ¹²⁵. This means that the medicine is presented for blessing with in adequate data on its quality, safety, and efficacy. Although plant- grounded composites have shown be less poisonous compared to conventional synthetic composites, there's growing substantiation on the side effects of the limited use of these plants against different conditions. The problem is that there’s inadequate data available regarding the quality, safety, and efficacy of herbal medicines. F. indica, for case, has shown potent extract against breast cancer when tested in the MDA- MB- 231 cell line. F. indicia is used traditionally to treat numerous diseases and people have indeed started the use of its herbal tea against breast cancer. Still, the question remains that there are only a many reports available on the anticancer activity of the plant. Encyclopedically, the process of oncology medicine development and marketing is regulated through the involvement of experts and a premonitory process intermediated by nonsupervisory authorities ¹²⁶. There are several nonsupervisory frame models available for defining similar medicines but there's a need for harmony among regulating agencies and enhancement in the regulation process. For case, the FDA has lately espoused the questions and answers guidelines of the International Council for Adjustment on the nonclinical evaluation of medicines intended to treat cancer. These guidelines include 41 questions and answers which give fresh information about anticancer medicine development and are aimed at bringing adjustment in the process of anticancer medicine development ¹²⁷.

Modern   Trends   in   Traditional   Medicine   Informatics   and Opportunities for Anticancer Plant Products: With the advancement of information technology and bioinformatics, there's an adding trend to make resources and databases that report herbal formulations, active components of the herb, and affiliated information.

There are several efforts like Chinese Medicine Integrated Database (TCMID) ¹²⁸, Collaborative Molecular Conditioning of Useful Plants (CMAUP) ¹²⁸, SymMap ¹²⁹, encyclopedia of traditional Chinese drug( ETCM) ¹³⁰ etc. In addition, several experimenters have developed strategies for in-silico pharmacokinetic properties of motes/ medicines ^131-136.

Similar approaches are also applicable to phytochemicals and plant- grounded active medicine factors for their virtual webbing, possible mode of action, and advanced medicine discovery ^137-139. Several factory- grounded anticancer composites have been estimated using in-silico and systems pharmacology tools ^140-146.

The current study encourages farther studies on anticancer active constituents (of factory origin) for their in-silico webbing and pharmacokinetic conditioning. Considering the fact that factory- grounded medicine phrasings generally consists of several phytochemicals or indeed further than one shops. The major challenge on this direction would be to prognosticate the role of phytochemicals other than active composites and are present in the traditional drug.

COCLUSION: From the present review, it can be concluded that herbal medicinal plants and their derivations are active against colourful type of cancers like lymphomas, breast, ovarian, lung, liver, and stomach, prostate and testicular cancers. The cheap herbal medicinal treatment which may largely be recommended to the pastoral and poor people especially of developing countries to treat effectively the cancers of different type is an ideal choice.

The delved traditional medicinal plants in this composition could be a key to identify the composites with anti-cancer effects; thus, if their composites are examined, they might help to develop new, more effective medicines, in addition to contributing to identify the main mechanisms involved in cancer. This detailed analysis of different shops showed that medicinal sauces promise a huge anticancer eventuality.

This composition exhaustively highlights the medium of antitumor action of some of the important plants. This is generally done through regulating signaling pathways. Numerous studies have reported inhibition of enzymes that stops excrescence growth. These studies are substantially performed in mortal cell lines. It’s stressed that these plants play an important anticancer part through their different classes of secondary metabolites.

TABLE 2: SOME OF THE IMPORTANT ANTICANCER MEDICINAL PLANTS, THEIR ACTIVE COMPONENTS, AND IN-VITRO AND IN-VIVO ACTIVITY

ACKNOWLEDGMENTS: The authors wish to gratefully acknowledge and thank the following for their generous support of this review: Dr. Shashi Alok assistant professor in Institute of Pharmacy Bundelkhand University Jhansi Uttar Pradesh.

CONFLICTS OF INTEREST: The authors declare no conflict of interest.

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     How to cite this article:

     Saddam, Suman and Alok S: Anti-cancerous activity of medicinal plants. Int J Pharm Sci & Res 2023; 14(5): 2236-52. doi: 10.13040/IJPSR.0975-8232.14(5).2236-52.

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