The Current State of Knowledge in Biological Properties of Cirsimaritin

The search for natural plant-based products as new pharmacological alternatives to treat various human pathologies has taken on great importance for researchers and research laboratories. In this context, research has intensified to extract and identify natural molecules endowed with biological effects. The objective of this study is to review the source and pharmacological properties of cirsimaritin. The identification and isolation of this flavonoid from various natural sources, including medicinal plants such as Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and Ocimum sanctum, has been carried out and verified using different spectral techniques. Biological effect investigations are carried out with a wide variety of experimental models in vitro and in vivo and laboratory techniques. The results of these research works showed the biological properties of cirsimaritin including anticancer, antimicrobial, antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms involved in the multiple activities of this molecule are diverse and include sub-cellular, cellular, and molecular levels. Indeed, this bioactive induces anti-inflammatory and antiproliferative effects by inhibiting cell membrane receptors, interference with signaling pathways, and inhibiting transcriptional factors such as Nf-κB involved in cell promotion and proliferation. In the light of these results, cirsimaritin appears as a promising and viable alternative natural bioactive drug to treat many pathological conditions.


Biological and Pharmacological Properties
In vitro and in vivo investigations concerning cirsimaritin have shown multiple biological and pharmacological properties ( Figure 2). These induced activities are due to the different mechanisms mediated by this substance. In these following sections, the pharmacological effects as well as the associated mechanisms of this compound will be described, highlighted, and discussed.

Biological and Pharmacological Properties
In vitro and in vivo investigations concerning cirsimaritin have shown multiple biological and pharmacological properties ( Figure 2). These induced activities are due to the different mechanisms mediated by this substance. In these following sections, the pharmacological effects as well as the associated mechanisms of this compound will be described, highlighted, and discussed.

Antibacterial and Anti-Fungal Activities
The first research reporting the antimicrobial properties of cirsimaritin dates back to 1983 (Table 2). Miski et al. [78] investigated the antibacterial effect of Salvia palaestina against negative and positive gram bacteria. The results showed that cirsimaritin was the only flavonoid with the highest antibacterial activity against Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus vulgaris, Staphylococcus aureus, and Staphylococcus epidermis using the disk diffusion method. In another study reported by Ragasa et al. [28], cirsimaritin was found to be active against the fungi aspergillus niger, Candida albicans, and trichophyton mentagrophytes, and, with activity indices of 0.3, 0.3, and 0.4, respectively. However, cirsimaritin showed weak antimicrobial activity and was even inactive against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. Similar results were recorded by Rijo et al. [29] on the antimicrobial effect of cirsimaritin using micro-dilution and agar diffusion methods to determine Minimum Inhibitory Concentrations (MICs) and the diameter of inhibition zones, respectively. The authors showed that the most resistant pathogen to cirsimaritin was Escherichia coli, moreover this molecule did not inhibit Candida albicans, Mycobacterium smegmatis, and Pseudomonas aeruginosa, while an anti-Staphylococcus aureus and anti-Enterococcus hirae effect was observed. A study by Marino et al. [30] found that cirsimaritin, one of the major constituents of Asphodeline anatolica acetone extract, exhibits an antibacterial effect against Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus.

Antibacterial and Anti-Fungal Activities
The first research reporting the antimicrobial properties of cirsimaritin dates back to 1983 ( Table 2). Miski et al. [78] investigated the antibacterial effect of Salvia palaestina against negative and positive gram bacteria. The results showed that cirsimaritin was the only flavonoid with the highest antibacterial activity against Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus vulgaris, Staphylococcus aureus, and Staphylococcus epidermis using the disk diffusion method. In another study reported by Ragasa et al. [28], cirsimaritin was found to be active against the fungi aspergillus niger, Candida albicans, and trichophyton mentagrophytes, and, with activity indices of 0.3, 0.3, and 0.4, respectively. However, cirsimaritin showed weak antimicrobial activity and was even inactive against Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. Similar results were recorded by Rijo et al. [29] on the antimicrobial effect of cirsimaritin using micro-dilution and agar diffusion methods to determine Minimum Inhibitory Concentrations (MICs) and the diameter of inhibition zones, respectively. The authors showed that the most resistant pathogen to cirsimaritin was Escherichia coli, moreover this molecule did not inhibit Candida albicans, Mycobacterium smegmatis, and Pseudomonas aeruginosa, while an anti-Staphylococcus aureus and anti-Enterococcus hirae effect was observed. A study by Marino et al. [30] found that cirsimaritin, one of the major constituents of Asphodeline anatolica acetone extract, exhibits an antibacterial effect against Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus.
Significant antimicrobial effect of Centaurea pseudosinaica extract, with cirsimaritin as one of the main components, was recorded using the micro-dilution technique, against human pathogens such as Aspergilus fumigatus, Candida albicans, Geotrichum candidum, and Syncephalastrum racemosum, and Gram-positive (Bacillis subtilis and Streptococcus pneumoniae) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The results obtained clearly revealed an excellent efficacy of the alcoholic extract against all micro-organisms, especially against Candida albicans [51]. Interestingly, Ren and co-workers observed the antimicrobial activities of cirsimaritin identified in the bark of Tamarix ramosissima on Bacillus cereus, Escherichia coli, Staphylococcus aureus, Listeria monocytogene, Pseudomonas aeruginosa, Salmonella typhimurium, and Shigella castellani using the disk   Significant antimicrobial effect of Centaurea pseudosinaica extract, with cirsimaritin as one of the main components, was recorded using the micro-dilution technique, against human pathogens such as Aspergilus fumigatus, Candida albicans, Geotrichum candidum, and Syncephalastrum racemosum, and Gram-positive (Bacillis subtilis and Streptococcus pneumoniae) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The results obtained clearly revealed an excellent efficacy of the alcoholic extract against all microorganisms, especially against Candida albicans [51]. Interestingly, Ren and co-workers observed the antimicrobial activities of cirsimaritin identified in the bark of Tamarix ramosissima on Bacillus cereus, Escherichia coli, Staphylococcus aureus, Listeria monocytogene, Pseudomonas aeruginosa, Salmonella typhimurium, and Shigella castellani using the disk diffusion method. The inhibitory effect of the bark extract on bacterial pathogens was appreciable. Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus are more sensitive to the bark extract than Escherichia coli, Pseudomonas aeruginosa, Salmonella typhimurium, and Shigella castellani. Among these bacteria, L. monocytogenes was the most damaging bacteria with the lowest MBC value (10 mg/mL) [83].

Antiviral and Antiparasitic Activities
Cirsimaritin was also studied for its activities against viruses. Indeed, Yan et al. [34] tested cirsimaritin on the influenza virus and its mechanism effect. A concentrationdependent reduction of viral titers, protein synthesis, and influenza A virus (IAV) RNA after cirsimaritin treatment has been demonstrated. From the point of view of the mechanism, the team suggests that the inactivation of the NF-κB/p65 signal pathway might be the origin of cirsimaritin-induced inhibition of IAV. In a computer-aided research, Hussain et al. [89] studied the cirsimaritin effect, isolated from Santolina insularis, on chikungunya virus (CHIKV) replication by targeting the non-structural proteins from CHIKV (nsP4, nsP3, nsP2, and nsP1). As results, cirsimaritin has shown a strong binding affinity on nsP1 compared to others.
Regarding the recent outbreaks of dangerous viruses namely COVID-19 with a rapid spread and which the development of new anti-viral drugs represents a main challenge. In this context, cirsimaritin was tested, in silico, against spike Protein SARS-CoV-2 [90]. According to this research, Cirsimaritin shows moderate binding affinity against the target protein.

Antioxidant Activity
Cirsimaritin represent an important benefic health molecule used in pharmaceutical industries to produce antioxidants and products against free radicals (Table 3). A study performed by Ibañez et al. [35] using DPPH assay revealed that the extracted compounds from Rosmarinus officinalis leaves, containing the flavonoid cirsimaritin showed high antioxidant activity. Similar results were obtained by a study investigated by Jipa et al. [36], who evaluated the antioxidant activity of Rosmarinus officinalis extract after γ-irradiation. It has been showed in this study that the cirsimaritin present in R. officinalis extract possess a good antioxidant property which enhanced by high-energy irradiation. Likewise, Cavero et al. [71] demonstrated the antioxidant efficiency of Rosmarinus officinalis extract on 1, 1-Diphenyl-2-picrylhydrazyl (DPPH). In this study, cirsimaritin was identified as one of the most important flavonoids in the extract, but the correlation matrix established by the authors, showed that this molecule is poorly correlated with the antioxidant activity (EC 50 values). Furthermore, Kelm et al. [27] demonstrate using an antioxidant assay performed by analyzing the oxidation of model liposomes by fluorescence spectroscopy that cirsimaritin extracted from Ocimum sanctum surprisingly displayed poor antioxidant activity. Similarly in another study, Kolak et al. [93], demonstrated that cirsimaritin from Salvia poculata extract did not have antioxidant properties using β-carotene bleaching, ABTS cation radical scavenging activity and superoxide anion radical assays. Ben Sghaier et al. [86] demonstrated that cirsimaritin extracted from Teucrium ramosissimum showed an excellent antioxidant capacity at a Teac value of 2.04 µM using the ABTS. Lee et al. [53] studied the antioxidant effect of cirsimaritin isolated from Korean thistle (Cirsium japonicum) against DPPH. Results suggest that cirsimaritin showed potential reduction of DPPH free radicals with percentages of inhibition between 80% and 100% at a concentration of 100 µg/mL. The antioxidant capacity was observed to be significantly higher in the extract of Artemisia Judaica which is a rich source of cirsimaritin [94]. Another study by Fattahi et al. [57] evaluated the antioxidant potency of cirsimaritin identified among 13 natural populations of Dracocephalum kotschyi using the ferric reduction capacity of plasma (FRAP). The results indicate that the antioxidant ability of the plant extracts was mostly due to the surface flavonoids, notably the cirsimaritin flavonoid for which the concentration varies from 97.38 to 637.66 µg/g DW leading to a high antioxidant activity ranging from 203.39 to 681.27 µmol Fe 2+ /100 g DW. Burki et al., [95] found that the Monotheca buxifolia bark extract which contain cirsimaritin as an active compound showed significant antioxidant effect against DPPH, superoxide and hydrogen peroxide with respectively an inhibition percentage of 89.55, 82.10 and 80.55% at a concentration of 500 µg/mL. Dawé et al. [56] investigated the antioxidant effect of cirsimaritin isolated from Combretum fragrans extract. The authors showed that cirsimaritin presented potent DPPH radical scavenging activity with a reported IC 50 value of 55.9 µM.  Two other research works conducted separately by Al Ati et al. [38] and Cottiglia et al. [68] on cirsimaritin, isolated from traditionally used medicinal plants, showed a very significant anti-inflammatory activity. In the same context, another research study carried out by Kelm et al. [27] evaluated the cyclooxygenase (COX) inhibitory activity of cirsimaritin, at concentrations greater than 1000 µM, purified from the extract of fresh stems and leaves of Ocimum sanctum, while comparing with naproxen, ibuprofen and aspirin at concentrations of 10, 10, and 1000 M, respectively.
During the research performed by Kuo et al. [96], rosemary (Rosmarinus officinalis) Cirsimaritin also caused the blockage of the production of different cytokines including IL-6, IL-10, IL-6, IFN-γ, and TNF-α, as well a decrease in NO production in a dose-dependent manner in RAW264.7 via the repression iNOS expression (Figure 3) [32]. It also suppressed the activation of the transcription factors induced by LPS, namely c-fos, STAT3. From these findings, this flavonoid may have an anti-inflammatory effect, which is regulated by the phosphorylation of STAT3 and the inhibition of c-fos in RAW264 cells. This inhibition of gene expression induces a decrease of cyclooxygenase-2 (COX-2) and Myeloperoxidase (MPO) (Figure 3).
Two other research works conducted separately by Al Ati et al. [38] and Cottiglia et al. [68] on cirsimaritin, isolated from traditionally used medicinal plants, showed a very significant anti-inflammatory activity. In the same context, another research study carried out by Kelm et al. [27] evaluated the cyclooxygenase (COX) inhibitory activity of cirsimaritin, at concentrations greater than 1000 µM, purified from the extract of fresh stems and leaves of Ocimum sanctum, while comparing with naproxen, ibuprofen and aspirin at concentrations of 10, 10, and 1000 M, respectively.
During the research performed by Kuo et al. [96], rosemary (Rosmarinus officinalis) extract containing cirsimaritin showed a dose-dependent effect on the expression of inflammatory mediators, in particular on lipid peroxidation. Nevertheless, the simultaneous connection of anti-inflammatory activity between rosemary extract (from SC-CO (2) at 5000 psi and 80 • C) and its pure carnosic acid (AC) via murine macrophage cells RAW 264.7 treated with LPS was determined. In addition, CA and SCCO (2) distinctly inhibited LPS-induced NO production, phosphorylated IkappaB (P-IκB), TNF-α, and NF-κB/p65 the inducible nitric oxide synthase (iNOS) and the expression of COX-2 ( Figure 3). From these data, it can be concluded that cirsimaritin exhibits a significant anti-inflammatory effect with better inhibitory activity on NO (IC 50 of 22.5 M or 7.47 g/mL) in comparison with the SCCO extract (IC 50 of 14.50 g/mL).

Antidiabetic Activity
Numerous studies have revealed the therapeutic potential of cirsimaritin in the treatment of diabetes. Research conducted by Stefkov et al. [85] investigated the biochemical mechanism of the insulinotropic and antihyperglycemic effects of T. polium extracts containing cirsimaritin. Therefore, an interesting insulinotropic effect on INS1E cells at a dose of 500 µg/mL is observed. After 8 h following administration, the doses of 125 mg/kg (the same doses of the extract) administered intra-gastrointestinally in hyperglycemic and normal rats were found to be more effective in lowering blood glucose compared to intraperitoneal injection (35% reduction vs. 24%) with a large effect (50% reduction). After a week and a half of treatment, the comparison of the effect levels following the administration of glibenclamide at 2.5 mg/kg (reduction of 38%), demonstrates the absence of effects on the blood lipid profiles. As for the oral glucose tolerance assay, the extract lowered blood sugar by about 35%. Consequently, it was found that treatment results in a decrease in hepatic glycogen and tends to normalize the effect of gluconeogenesis enzymes. In another study performed with virtual screening, cirsimaritin has good binding affinities for DPP-4 and, once DPP-4 will be blocked, insulin secretion will increase ( Figure 4) [33]. Moreover, by facilitating of Na/Ca exchange, cirsimaritin can modulate gene expression of several intracellular proteins involved in glucose metabolism regulation including PKC. It can also increase the expression of key factors involved in apoptosis preventing thus the pancreatic β cells from apoptotic depending on glucotoxicity and/or lipotoxicity (Figure 4).
In TNF-α-treated mouse FL83B hepatocytes, Xu et al. [73] investigated the mechanism by which the bioactive fractions from Ruellia tuberosa enhanced insulin resistance using a glucose uptake assay. Among them, EAF5-5 fraction, which contained syringic acid (27.3 µg/g), p-coumaric acid (95.0 µg/g), and cirsimaritin (805.5 µg/g) markedly improve glucose uptake. Those authors suggested that cirsimaritin may be considered as one major active ingredient from the EAF5-5 combination involved in the enhancement of glucose uptake rate of insulin-resistant FL83B hepatocytes. nism by which the bioactive fractions from Ruellia tuberosa enhanced insulin resistance using a glucose uptake assay. Among them, EAF5-5 fraction, which contained syringic acid (27.3 µg/g), p-coumaric acid (95.0 µg/g), and cirsimaritin (805.5 µg/g) markedly improve glucose uptake. Those authors suggested that cirsimaritin may be considered as one major active ingredient from the EAF5-5 combination involved in the enhancement of glucose uptake rate of insulin-resistant FL83B hepatocytes.

Anti-Cancer Activity
Several studies have been carried out on cell cultures showed that cirsimaritin exerts antiproliferative activities [97][98][99][100][101][102][103] on numerous cancer cell lines (Table 4). In this regard, Moghaddam et al. [97] studied, in vitro, the antiproliferative activity of cirsimaritin isolated from Dracocephalum kotschyi against normal and malignant cell lines using the MTT test. As results, this molecule showed a moderate inhibition of HT-29 and AGS cell lines proliferation compared to SaOs-2 and WEHI-164. Likewise, Bai et al. [63] have shown that the said substance also exhibits a moderate anti-proliferative activity on COLO-205 cells with IC50 values equal of 13.1 µM.

Anti-Cancer Activity
Several studies have been carried out on cell cultures showed that cirsimaritin exerts antiproliferative activities [97][98][99][100][101][102][103] on numerous cancer cell lines (Table 4). In this regard, Moghaddam et al. [97] studied, in vitro, the antiproliferative activity of cirsimaritin isolated from Dracocephalum kotschyi against normal and malignant cell lines using the MTT test. As results, this molecule showed a moderate inhibition of HT-29 and AGS cell lines proliferation compared to SaOs-2 and WEHI-164. Likewise, Bai et al. [63] have shown that the said substance also exhibits a moderate anti-proliferative activity on COLO-205 cells with IC 50 values equal of 13.1 µM.  Another study released by Sen et al. [50] indicates that cirsimaritin, isolated from the chloroform extract of Centaurea kilaea Boiss, exhibits significant anticancer activity, especially against breast cancer, and the value (0.5-50 µg/mL) was taken versus a normal cell line (L929, mouse fibroblast) and certain human cancer cell lines (cervical carcinoma, MCF-7, prostate carcinoma, PC-3, and breast carcinoma) using the MTT test with IC 50 value equal to 4.3 µg/mL.
Using an in vivo cancer model, Awad et al. [101] recorded an antitumor activity of this molecule (separated from Achillea fragrantissima extract), characterized by the decrease in tumor size which can be explained by its antioxidant activities, confirmed by the increase in serum rate of TAC and reduction in serum TNF-α ( Figure 5). Furthermore, the results of the histopathological examination demonstrated the induction of apoptosis.
exhibited an inhibition of the viability of HUVECs with a concentration-dependent manner, which showed it inhibited angiogenesis. This anticancer activity was assigned to decrease secretion of angiogenesis mediator vascular endothelial growth factor (VEGF). This inhibition induces a decrease PK3K, Raf, Src, and Erk which declined the rates of p-Akt and p-ERK in MDA-MB-231 cells, inducing thus a decrease of mTOR and causing an antiangiogenesis effect [106] (Figure 5).
In recent study, cirsimaritin antiproliferative efficacity has been tested in human cancer cell lines including HaCaT, A431, K562, MDA-MB-231, A549, COLO-205, MCF-7, Ha-CaT, K562, NCIH-520, and PC-3, and normal cell lines HEK 293, L132, and WRL-68 and in primary macrophages, by Pathak et al. [98]. It was found that cirsimaritin showed selective antitumor effect against NCIH-520 cell-line with IC50 = 23.29 µM, via increasing the apoptosis (10 and 100 µM). Moreover, cirsimaritin also inhibits the action of CATD and ODC which is responsible for the development stage of the cancer cells. In addition to this, follow Lipinski's rule of five, it exerted a good binding score with the selected targets and it non-mutagenic.

Other Biological Activities
Many biological activities can be linked with the use of cirsimaritin. Indeed, cirsimaritin inhibits the amplitude of the phasic contractions of guinea-pig ileum [108]. Furthermore, Hasrat et al. [26] demonstrated that cirsimaritin induces an adenosine antagonistic effect in rats. These results suggest that the interaction between the cirsimaritin and adenosine receptor could result in inhibition of calcium and sodium transport. According to these researchers, this flavonoid-molecule could have a beneficial effect in acute renal failure.  [99]. They showed that this cirsimaritin of synthetic origin exhibits an important antitumor activity and caused mitochondrial apoptosis in GBC-SD cells via activating caspase-4, -9, and -3 cascades, changing the mitochondrial membrane potential. Furthermore, cirsimaritin lead to the generation of reactive oxygen species in GBC-SD cells which triggers ER stress mitochondrial apoptotic pathways in GBC-SD cells. These molecular events induce an intrinsic apoptosis depending on caspases activation and ROS ( Figure 5).
In another study, cirsimaritin as a major component of Cirsium japonicum var. maackii, exhibited an inhibition of the viability of HUVECs with a concentration-dependent manner, which showed it inhibited angiogenesis. This anticancer activity was assigned to decrease secretion of angiogenesis mediator vascular endothelial growth factor (VEGF). This inhibition induces a decrease PK3K, Raf, Src, and Erk which declined the rates of p-Akt and p-ERK in MDA-MB-231 cells, inducing thus a decrease of mTOR and causing an anti-angiogenesis effect [106] (Figure 5).
In recent study, cirsimaritin antiproliferative efficacity has been tested in human cancer cell lines including HaCaT, A431, K562, MDA-MB-231, A549, COLO-205, MCF-7, HaCaT, K562, NCIH-520, and PC-3, and normal cell lines HEK 293, L132, and WRL-68 and in primary macrophages, by Pathak et al. [98]. It was found that cirsimaritin showed selective antitumor effect against NCIH-520 cell-line with IC 50 = 23.29 µM, via increasing the apoptosis (10 and 100 µM). Moreover, cirsimaritin also inhibits the action of CATD and ODC which is responsible for the development stage of the cancer cells. In addition to this, follow Lipinski's rule of five, it exerted a good binding score with the selected targets and it non-mutagenic.

Other Biological Activities
Many biological activities can be linked with the use of cirsimaritin. Indeed, cirsimaritin inhibits the amplitude of the phasic contractions of guinea-pig ileum [108]. Furthermore, Hasrat et al. [26] demonstrated that cirsimaritin induces an adenosine antagonistic effect in rats. These results suggest that the interaction between the cirsimaritin and adenosine receptor could result in inhibition of calcium and sodium transport. According to these researchers, this flavonoid-molecule could have a beneficial effect in acute renal failure.
Similarly, Abdelhalim et al. [70] reported that cirsimaritin exerted significant antinociceptive and anxiolytic effects which the anxiolytic activity may be mediated via GABAA receptor, without any signs of acute toxicity (50-200 mg/kg). The anxiolytic-like activity cirsimaritin in mice was also reported by González-Trujano et al. [109]. At a concentration of 3 mg/Kg (i.p), the number of head-dips was decreased by this substance and the lapse of open arms was increased in the hole-board and in the plus-maze tests, respectively. Furthermore, Wang et al. [110] studied the inhibition of cirsimaritin on a formyl-methionylleucyl-phenylalanine-(fMLP) excited respiratory burst in rat neutrophils. Those researchers observe that it is probably that cirsimaritin inhibits the fMLP-caused respiratory burst in vivo via the closure of the phos-pholipase D (PLD) signalling pathway.
The protective effect of cirsimaritin from Korean thistle on apoptosis induced by STZ is documented by Lee et al. [103]. Their results, in pancreatic b cells, proved that cirsimaritin potentially removed apoptosis via increasing anti-apoptotic BCL-2 protein expression and reducing the activation of both caspases 8 and 3, BID and the DNA repair protein poly (ADP-ribose) polymerase (PARP).
Earlier study reported by Kim et al. [102] on the hyperpigmentation activity of cirsimaritin (isolated from Lithocarpus dealbatus branches) and explained the mechanism by which cirsimaritin stimulate melanogenesis in B16F10 cells (murine melanoma cells). The author's findings indicate that this molecule stimulates the expression of tyrosinase by activation of cAMP/PKA signaling, subsequent phosphorylation of CREB, tyrosinase, TRP1 expression, and upregulation of MITF which further triggers melanogenesis.

Conclusions and Perspectives
Natural compounds have considerable benefits when evaluated for their biological effects. In this order, these molecules have been studied with a view to develop new therapeutic options to treat human diseases. According to the present review, many chemical analysis techniques revealed the presence of this flavonoid in a variety of pharmacologically active plants including Artemisia judaica, Cirsium japonicum, Lithocarpus dealbatus, Microtea debilis, and other species. In addition, different pharmacological and biological properties were investigated and the results showed that cirsimaritin has: a broad spectrum of action on a variety of pathogenic microorganisms in humans (Gram-positive and -negative bacteria, and fungi); anticancer effects against human colon carcinoma (HT-29), human gastric adenocarcinoma (AGS), human osteosarcoma (SaOs-2), murine fibrosarcoma (WEHI-164) and human fetal foreskin fibroblast (HFFF-P16), MCF-7, and PC-3 cell lines; and antidiabetic, antiparasitic, antioxidant, and anti-inflammatory effects. The mechanisms of action of cirsimaritin are not well understood, but it seems, according to the research highlighted, that this compound can exhibits its effects at different levels as it has been described above. Furthermore, further pharmacodynamic investigations should be conducted on cirsimaritin aimed at determining of its exact mode of action. Moreover, pharmacokinetic studies should also be conducted, on the one hand, to validate its: absorption, availability, metabolism, and elimination; on the other hand, to validate its safety via toxicological tests. Moreover, other perspectives concerning clinical trials of cirsimaritin against chronic inflammation would be a very proposing research perspectives to develop anti-inflammatory drugs. Moreover, a combination of cirsimaritin as an anticancer agent with used drugs in chemotherapy can give important results about the potent combinatory effects.