Phytochemical Composition and Pharmaceutical Potential of Lantana sp: A Review

Lantana is a common plant found in around 60 tropical and subtropical countries worldwide. It is a highly invasive species that has tremendously dominated over other species of plants and threaten biodiversity. At present, physical, chemical, and biological agents are in consideration to eradicate this plant to prevent the threat to biodiversity and soil fertility. Lantana is considered as an unwanted plant and its biomass is disposed off. In this review, the pharmaceutical potential of this plant and its phytochemical constituents are discussed. Being source for wide variety of bioactive phytochemicals, Lantana is a valuable pharmaceutical raw material. Hence, instead of eradicating the plant as waste material, its pharmaceutical potentials such as antioxidant, antidiabetic, antimicrobial, anti-inflammatory, and anticancer activities can be exploited for the possible application as therapeutic agent. The modern medicine can take advantage of the fast-growing nature of this plant and use this plant as a tool for biopharming. In traditional medicine, Lantana has been used in formulation along with other plants as a treatment for several ailments. This review concludes that Lantana is a medicinally valuable plant, with huge potential in the pharmaceutical industry.


INTRODUCTION
T he genus Lantana is from the Verbenaceae family, Lantana camara was introduced in India, for its ornamental and attractive nature. [1] It is called a wild sage because of its toxicity, and it outcompetes with other most desirable species of flora and fauna. It is considered one of the important medicinal plants in the world. Lantana is widely used as folk medicine in many states and in and around India and Bangladesh. Phytochemical investigation has resulted in the isolation of various bioactive phytochemicals from different parts of the plant. [2] Therefore, the aim of the present review is to provide a complete compilation of the phytochemical components of Lantana recorded in the literature. [3] The biological activities of L. camara were reviewed based on their scientific reports in recent years. [4,5] All reported phytochemical constituents of Lantana plant are summarized in Table 1 with their molecular weight and chemical structure for further discussion. The appearance of L. camara with its flower and leaf is shown in Figure 1.   epi-cubebol, cis-3-hexen-1-ol, and 1-hexanol are the major compounds found in Lantana. [8]

APPLICATIONS OF KNOWN PHYTOCHEMICALS
All reported molecules from Lantana have been known to have many pharmaceutical activities. The following is list of known activities of reported phytochemicals from Lantana.

Betulinic acid
It exhibits therapeutical activities against breast cancer cells and normal fibroblast cells. [9] It also acts as an antimelanoma agent. [10] Beta-curcumene It is a type of sesquiterpene. [11] Betulonic acid Ionic derivatives of betulinic acid show better biological activities and are more soluble in water. It exhibits antiviral activity and works against the herpes simplex virus type-2. [12] Camaric acid It is isolated from the methanolic extract of Lantana involved in the nematicidal activity. [13] Icterogenin It is involved in changing the rate of bile flow in mice. [14] Katonic acid It is a cytotoxic triterpene which acts as a plant anticancer agent. [15] Lantadene A It is also called as rehmannic acid. It is the active principle of L. camara L. which has certain oxygen functions. [16] Lantoic acid It is a pentacyclic triterpenoid involved in nematicidal activity found from the aerial parts of Lantana. [17] Luteolin It suppresses the growth and metastasis of human lung cancer cells. It possesses antitumor, anti-inflammation, anticancer, and antioxidant activities. [18] It is a type of flavonoid which induces the immunomodulatory response in peripheral blood mononuclear cells. [19] It is a type of polyphenolic flavone that stimulates the antitumor effect of cisplatin in drug-resistant ovarian cancer through inhibition of cell metastasis and programmed cell death. [20] It has chemo stimulating and antiproliferative on human gastric cancer cell lines. [21] It also reduces obesityassociated insulin resistance in mice by certain signaling in adipose tissue macrophages and is also involved in insulin resistance. [22] Martynoside These plant phenylpropanoid glycosides consist of antimetastatic, anticancer, and cytotoxic activities. It can also be considered as natural selective estrogen receptor modulator. [23] It also helps in retarding the skeletal muscle fatigue depending on their antioxidant activities. [24]

Oleanolic acid
It possesses diverse pharmacological activities and a naturally occurring pentacyclic triterpene, it inhibits the cell proliferation and cell survival of prostate cancer cells. [25] It also suppresses the proliferation of lung carcinoma cells, which indicates its antitumor activity. [26] Its combination with metals such as iron or zinc possesses significant antiinflammatory, immunomodulatory, and antiasthma activity. [27] p-Coumaric acid It is a type of cinnamic acid which has antioxidant activity. It can also prevent bone loss, thereby promotes osteoblastogenesis. [28] It also possesses antiproliferative effect on colon cancer both in vitro and in vivo. [29] p-Hydroxybenzoic acid It is used as a fungicide, it has potential biotechnological application in food, pharmacy, cosmetics, etc. [30] Pomolic acid Competitive antagonist of norepinephrine and adenosine triphosphate induced aggregation of human platelets. [31] Salicylic acid It is a key plant hormone that is involved in hosting response against microbial infections. [32] Theviridoside It is found in the roots of the L. camara. [6] It also shows cytotoxicity towards human cancer cell lines. [33] Ursolic acid It is a plant-based pentacyclic triterpenoid carboxyl acid, against vascular endothelial damage, and liver oxidative injury in the mice. [34] It also acts as an effective neuroprotective drug against the inflammatory responses on the cerebral region of the brain. It can act as an inflammatory agent. [35] PHARMACOLOGICAL ACTIVITIES OF LANTANA

Anti-inflammatory activity
Leaf extract of Lantana possesses phytochemicals like terpenoids (mainly triterpenes and sesquiterpenes) that are cytotoxic on tumor cells and exhibited anticancer potential in animal models. Therefore, the extraction of triterpenoids for drug development is useful because of its many biological activities. [36] There are around 70 triterpenes isolated from this genus. The methanolic extract of this plant has been reported to reduce the carrageenan-induced paw edema. Antiinflammatory agents can suppress seizures in humans and involve in the process of epileptogenesis. It can also induce the cytokine encoding genes, which suppresses inflammation. Based on these attributes, Lantana plant is considered to be significantly anti-inflammatory in nature.

Antioxidant activity
Antioxidant property is a fundamental factor of all food substances. It is estimated in terms of reducing potential and free radical scavenging exercises. [37] It benefits by counteracting the degenerative ailments through oxidative mechanisms. Extracts of Lantana leaves are proven to be rich in flavonoid content. There are around 30 flavones isolated from Lantana species. These flavones are also believed to activate certain antioxidant response systems in the cell system which helps in scavenging reactive oxygen molecules from the cell. Phenolic compounds such as caffeic acid and rosmarinic acid are reported to be teeming compounds in the methanolic extract of Lantana, which contributes to the antioxidant nature of the plant. There are many varieties of Lantana leaf extract which shows the free radical scavenging activity and in vitro lipid peroxidation. Thereby, it prevents certain human diseases such as myocardial infection, cancer, and rheumatoid arthritis. [38] Verbascoside is the major phenolic compound present in the species of Lantana (Lantana montevidensis) which helps in preventing the disease named Konzo which is related to oxidative damage. [39] These reports support the fact that Lantana is a potential source of antioxidant molecules.

Antimicrobial activity
Compounds like flavones isolated from the leaves of Lantana species possess antifungal and antibacterial properties. [40,41] Known for its bioactive molecules, Lantana also readily kills off the bacteria, aiding to its antibacterial activity. [3] Extracts of these plants are also proven to treat gastrointestinal infections. [42] Lantana is also proven to exhibit antifungal activity against selected fungal strains. [42] The main components of the essential oil of Lantana species consist of E-nerolidol, phytol, and E-caryophyllene which provide resistance to many fungal pathogens. [42] This is a potential source for further exploitation, as there is only handful of research done in this aspect of the plant.

Anticancer activity
Anthraquinones are reported to be present in Lantana.
Anthraquinones are commercially used in many pharmaceutical industries as an anticancer agent. This suggests a potential anticancerous application of Lantana.
The phenolic compounds of this plant have been reported to help in cancer prevention. It is also proven to inhibit the proliferation of cancer cells. [43] L. camara has shown cytotoxic effects on cancer cell lines at low concentrations. It shows the potential of the plant to be used in treatment. [42] Antidiabetic activity Saponins present in the extract of Lantana are proven to help in reducing the blood glucose level. It is also proven to decrease the blood cholesterol level. It further helps in promoting general health. [44] Cardiac activity The presence of cardiac glycosides inside Lantana is one of the important features proven to be involved in the treatment of cardiac rhythm disorder and congestive heart failure. There are around 16 phenylethanoid glycosides and eight iridoid glycosides isolated from the same species. These proved that the phytochemicals in Lantana plant can be used in treating heart ailments and disorders.

Anti-insecticidal activity
Besides the venture as a psychoactive medication, alkaloids deduced from Lantana are used as insecticides which have significant toxicity toward insects. [45,46] Leaves and flower extracts of Lantana have been proven to have larvicidal activity. The essential of the leaves of Lantana was found to be repulsive for mosquitoes (Aedes aegypti L.). Combination of L. camara plant with other plants is reported to act as a mosquito repellent. [18] Essential oils present in the blades of Lantana have been proven to have insecticidal effects on vectors of dengue, malaria, dengue hemorrhagic fever, Chikungunya, and yellow fever. [17] These attributes of Lantana can potentially be exploited in developing insecticides for agricultural usage and developing topical mosquito repellents.

Anthelmintic activity
Leaves of Lantana species have been proved to be effective in anthelmintic property. Ethanolic extracts of Lantana species have been observed to be highly effective against certain worms like Pheretima posthuma. [47] Extracts of Lantana have shown antihelminthic activity against Fasciola hepatica as well, which causes hepatical disease to many domestic animals leading to death and thereby severe economic loss. [48] Antipyretic activity Ethanolic extract of Lantana plants has been observed to be antipyretic in nature. It lowers the temperature of the body by inhibiting the synthesis of prostaglandins. [49] Extracts of Lantana montevidensis have also demonstrated antipyretic activity. [39] Antispasmodic activity Oleanolic acid has been isolated from Lantana which is used by folk medicine practitioners from Bangladesh as an antispasmodic agent. [50] Antidiarrheal activity The stem of the L. camara has been used traditionally in the treatment of diarrhea. Scientific analysis proved that administration of L. camara causes a significant defect in the frequency and the weight of defecation.
Ethnopharmacological studies have shown that it has biological activity (antibacterial) against bacteria, causing diarrhea. [51] Lantana is also proven to have unique laxative and combustible properties.

CONCLUSION
L. camara is widely used in the conventional medicine system for the remedy of itchiness, wounds, boils, blisters, bilious fever, cataract, and inflammation, including rheumatism. Diverse parts of the flowers are used in the treatment of cold, neuralgia, chickenpox, eyesores, whooping cough, asthma, bronchitis, and arterial hypertension. L. camara has been reliably studied for numerous curative activities such as antioxidant, antibacterial, antipyretic, larvicidal, insecticidal, antimicrobial, wound healing, and antihyperglycemic potential. With many proven biological activities, Lantana is definitely a valuable medicinal plant, it can be used for drug development.
Lantana has been an invasive plant since many times, which affects biodiversity to a large extent every year. Due to the alarming rate of the spread of this invasive species, particularly in the tropical and the subtropical countries such as India and South Africa, these countries are currently focussing on eradication of this plant by pruning, burial, and burning. Instead, this plant can be used in therapeutic applications based on their phytochemical constituents and pharmaceutical value of the palnt. This review suggests that rather eradicating the plant from its existence, it can be uprooted and used as raw materials to extract pharmaceutically valuable bioactive phytochemicals.