Systematic Review: Phytochemical Content and Pharmacological Effects of Chrysanthemum Sp.

Chrysanthemum sp is a plant that is often used by the community as an ornamental plant, drink and traditional medicine. This study aims to examine the plant Chrysanthemum sp from the aspect of phytochemical and pharmacological activity. The review method used in this study is the PRISMA method. Sources of data obtained using databases electronic from PubMed and Google Scholar. The results of this review show that plants Chrysanthemum sp have phytochemical and pharmacological potential. The compounds contained in the plant Chrysanthemum sp are morphine, genistein , hydantoin , limonene, g-terpinene, a-pinene, a-terpenyl acetate, 4-terpenyl acetate, a-calacorene, a-cedrene, b-bourbobene, elemol, 2-hexenal, and orphenadrine . Chrysanthemum plants have anticancer, antibacterial, antioxidant, antifungal, analgesic, anti-inflammatory and anticonsulvan activities.


Introduction
Chrysanthemum sp is a type of plant that is in great demand by the public and is often used as an ornamental plant. A part from being an ornamental plant, chrysanthemum also has the potential as a medicinal plant. The group of chemical compounds contained in chrysanthemum plants are flavonoids, alkaloids, tannins, and terpenoids (Jung, EK 2009).
Previous literature mentions that the plant Chrysanthemum sp contains phytochemicals that have potential as drugs. These phytochemicals are reported to have antiallergic, antioxidant, and antimicrobial activity (Yang et al. 2017). However, in the previous literature review, comprehensive data on the phytochemical content, pharmacological effects and mechanism of action have not been presented. The purpose of this research is to examine the phytochemical aspects and pharmacological activities as well as the mechanism of action of the plant Chrysanthemum sp . of various species.

Method
The method used in this study is a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Sources of data were obtained from the database electronic PubMed, and Google Scholar. The keywords used are chrysanthemum, activity, secondary metabolites and chemical composition. The inclusion criteria used were articles from 2009-2021, using English and Indonesian. The type of article used is Original Article and the content of the manuscript that is relevant to the specified topic. Meanwhile, the research exclusion criteria were articles published before 2009 and Review Articles.
The search resulted in 209 articles which were then filtered according to the subject of the desired material, namely the phytochemical content and pharmacological effects of the plant Chrysanthemum sp so that 5 articles were selected for review. Furthermore, a comparison and analysis of the articles that have been obtained is carried out to be developed into a review article.

Taxonomy
Chrysanthemum sp is a plant that belongs to the division Spermatophyta with sub-division Angiospermae. Chrysanthemum sp belongs to the class Dycotiledonae, order Asterales, family Asteraceae, and genus Chrysanthemum. Chrysanthemum sp has several species including Chrysanthemum morifolium, Chrysanthemum maximum, Chrysanthemum daisy, Chrysanthemum indicum, and Chrysanthemum parthenium (Tjitrosoepomo, 2013

Botanical description
Plants Chrysanthemum sp has a white taproot. Stem height ranges from 0.5-1 m. The stem of Chrysanthemum sp is green, round, erect, and slightly branched, and has a rough surface (Andiani, 2013). Leaf Chrysanthemumsp is a type of single alternate leaves with pointed tip, base rounded shape, and has a bertoreh edge.leaves Chrysanthemum sp. green and has a rough surface.leaf size Chrysanthemum sp . ranging from 7-13 cm for leaf length, and 3-6 cm for leaf width (Andiani, 2013). Flower Chrysanthemumsp including compound interest form, which has a diameter of 3-5 cm.flower petals Chrysanthemum sp . cup-shaped, pointed tip, and has stamens and a fine pistil located in the middle of the flower, (Andiani, 2013).

Distribution of Geographic
Chrysanthemum sp found in Indonesia, Malaysia, China, Singapore, Australia, China, the Netherlands, Brunei, and Vietnam (Ekanantari, 2014). There are about 40 species of chrysanthemum scattered in Asia and Eastern Europe (Ryu, 2019).

Traditional Uses
Chrysanthemum sp is often used as a traditional medicine by the community. Dosage forms that are often made such as herbal drinks in the form of tea are believed to be able to treat health problems that occur in the community such as diseases caused by bacteria (Setiawati, 2019). In traditional Chinese medicine, chrysanthemum is used as an anti-inflammatory (Yang et al. 2017).

PROCEEDING 1 st International Pharmacy Ulul Albab Conference and Seminar (PLANAR)
Metabolite profiles performed using UPLC-QToF-MS/MS showed differences in metabolite profiles in roots, stems, leaves, and chrysanthemums. Typical compounds in the flower parts are morphine and in the leaves genistein and ethanolamine. The main compound in roots, stems, and leaves was Orphenadrine with a percentage of 9.11%, 10.16%, and 3.24%, respectively, and the main compound in the flower part was Morphine with a percentage of 10.86% (Listiyana, et al. al, 2019).

Results and Discussion
Based on the results of the article search, the authors found 5 articles that matched the topic to be reviewed. A summary of the articles is presented in table 1.

Bioactivity
Scientific evidence Chrysanthemum sp. Several pharmacological activities have been reported, namely, anticancer, antimicrobial, antioxidant, antifungal, analgesic, anti-inflammatory, and anticonvulsant. Each pharmacological activity and its mechanism are described as follows:

Anticancer Activity
Extracts of flowers, leaves, stems, and roots of Chrysanthemum sp is reported to have different chemical contents. These differences caused differences in cytotoxic activity in T47D cells. It is known that the lead compound from this plant is orphenadrine. There is a relationship between anticancer cytotoxic activity andlevels orphenadrine in each part of Chrysanthemum sp. The higher the levels ofcompounds orphenadrine in plants, the higher the anticancer potential (Listiyana, et al, 2019). Mechanism of orphenadrine in Chrysanthemum sp as an anticancer is to inhibit the work of cyclin dependent kinase (CDK) which is a cell cycle regulator through activating kinase, so that it can inhibit the formation of an active CDK-Cyclin complex (Mutiah et al, 2020). Inhibition that occurs through the action of the CKD-activating kinase enzyme

Antibacterial Activity
Essential oil fromleaves Chrysanthemum sp. showed antibacterial effect against Bacillus subtilis and Staphylococcus epidermidis, with anrange of 50 31.25-62.5 g/ml (Sassi, et al., 2014). The mechanism of action of monoterpenes as antibacterial is by diffusion into cells and damaging the structure of cell membranes (Sassi, et al, 2014).  (Sassi, et al, 2014).

Antioxidant activity
Of chrysanthemum leaf simplicia was reported to have antioxidant activity with an ICvalue of50 139.19 ppm. The IC50 value which is in the range of 50-200 ppm indicates the intensity as a strong antioxidant in chrysanthemum simplicia (Yulianti, 2019). The mechanism of action as an antioxidant is by donating hydrogen ions and then neutralizing the toxic effects of free radicals.

Antifungal Activity
The results collectively indicate that the antifungal properties of secondary metabolites leaves of C. morifolium partly be attributed to the content of some terpenoids, including zingiberene, -sesquiphellandrene, α-curcumene, (E) --farnesene, α-farnesene, and 1,8-cineole (Xue, et al, 2019). The mechanism of terpenoid derivatives in Chrysanthemum sp as an antifungal is by reducing the permeability of the cell membrane of microorganisms. Then it binds with protein and lipid molecules so that it affects the physiological function of cell membrane proteins and enzyme proteins (Komala, et al, 2019).

Analgesic activity
The analgesic effect of Chrysanthemum sp. has been reported using a pain model method involving peripheral and central mechanisms with acetic acid induction in experimental animals. extract Chrysanthemum trifurcatum (300 mg/kg) exhibited an analgesic effect with approximately 64% significant inhibition. The analgesic activity of extract is Chrysanthemum trifurcatum due to the presence of alkaloids and flavonoids in the extract Chrysanthemum trifurcatum (Salem, et al, 2019). The mechanism of action of alkaloids and flavonoids as analgesics is by inhibiting the cyclooxygenase and 5-lipoxygenase pathways so that arachidonic acid synthesis decreases (Salem, et al, 2019).  (Salem, et al, 2019).

Anti-inflammatory
Inflammatory activity The anti-inflammatory activity ofextract Chrysanthemum trifurcatum was evaluated by the percent inhibition of edema reduction performed in carrageenan-induced rats. Several comparisons between the tested groups revealed that oral administration ofextract Chrysanthemum trifurcatum at doses of 300 and 500 mg/kg showed a reduction in edema.extract Chrysanthemum trifurcatum at a dose of 300 mg/kg caused a significant reduction in leg edema at 5 hours post-administration. Meanwhile,extract Chrysanthemum trifurcatum at a dose of 500 mg/kg reduced leg edema at all test time points (Salem, et al, 2019). The mechanism of action of flavonoids inextract Chrysanthemum trifurcatum as an anti-inflammatory is to inhibit the formation of prostaglandins and cyclooxygenase (Salem, et al, 2019).

Analgesic
Inhibitors of the cyclooxygenase and 5lipoxygenase pathways that lead to a reduction in the formation of donut araki acid Flavonoids PROCEEDING 1 st International Pharmacy Ulul Albab Conference and Seminar (PLANAR) Figure 8. Mechanism of action of flavonoids as anti-inflammatory in Chrysanthemum (Salem, et al, 2019).

Anticonsulvan activity
Extract Chrysanthemum trifurcatum given to rats after being induced by Pentylenetetrazole revealed thatextract Chrysanthemum trifurcatum at a dose of 300 mg/kg had anticonsulvan activity.extract Chrysanthemum trifurcatum provided significant variation in latency time for clonic seizures (6.60 ± 0.67) and tonic seizures (9.92 ± 0.97). In addition,Extract Chrysanthemum trifurcatum significantly reduced mortality by 50% compared to 100% mortality in the control group (Salem, et al, 2019). The mechanism of action of hydantoin in Chrysanthemum trifurcatum as an anticonsulvan is to delay seizure induction by stimulating the GABA neurotransmitter so that it becomes active (Salem, et al, 2019).