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Bailly, C. Bioactive Phytochemicals from Ruta angustifolia Pers.. Encyclopedia. Available online: https://encyclopedia.pub/entry/41520 (accessed on 01 July 2024).
Bailly C. Bioactive Phytochemicals from Ruta angustifolia Pers.. Encyclopedia. Available at: https://encyclopedia.pub/entry/41520. Accessed July 01, 2024.
Bailly, Christian. "Bioactive Phytochemicals from Ruta angustifolia Pers." Encyclopedia, https://encyclopedia.pub/entry/41520 (accessed July 01, 2024).
Bailly, C. (2023, February 22). Bioactive Phytochemicals from Ruta angustifolia Pers.. In Encyclopedia. https://encyclopedia.pub/entry/41520
Bailly, Christian. "Bioactive Phytochemicals from Ruta angustifolia Pers.." Encyclopedia. Web. 22 February, 2023.
Bioactive Phytochemicals from Ruta angustifolia Pers.
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This entry is adapted from the peer-reviewed paper 10.3390/plants12040827

The genus Ruta in the family Rutaceae includes about 40 species, such as the well-known plants R. graveolens L. (common rue) or R. chalepensis L. (fringed rue), but also much lesser-known species such as R. angustifolia Pers. (narrow-leaved fringed rue). This rue specie, originating from the Mediterranean region, is well-distributed in Southeast Asia, notably in the Indo-Chinese peninsula and other territories. In some countries, such as Malaysia, the plant is used to treat liver diseases and cancer. Extracts of R. angustifolia display antifungal, antiviral and antiparasitic effects. Diverse bioactive natural products have been isolated from the aerial parts of the plant, notably quinoline alkaloids and furocoumarins, which present noticeable anti-inflammatory, antioxidant and/or antiproliferative properties.

anticancer agents furocoumarins Ruta angustifolia Ruta species

1. Quinoline Alkaloids

The presence of specific alkaloids in Ruta species was underlined more than 60 years ago with the isolation of the first furanocoumarin and furoquinoline alkaloids, such as dictamnine and evolitrine [1]. But these products were isolated mainly from R. graveolens L. and R. montana Mill. [2]. The presence and bioactivities of alkaloids in R. angustifolia Pers. was unambiguously established much later, in 2014 with the isolation of the quinolinone alkaloid pseudane IX and the characterization of its activity against the HCV virus [3]. Pseudane IX was found to inhibit HCV replication, predominantly at the post-entry step (IC50 = 3.0 µg/mL post-entry versus 11.5 µg/mL at the entry step, in Huh7.5 cells infected with HCV). The compound functions as an inhibitor of HCV RNA replication and viral protein synthesis. In the viral system used (HCV strain J6/JFH1-P47), pseudane IX turned out to be more potent that the reference product ribavirin (IC50 = 1.4 and 2.8 µg/mL, respectively) and the alkaloid only exerted a modest cytotoxic action (CC50 = 26 µg/mL).
The case of the furoquinoline alkaloids, kokusaginine merits a mention because the compound, found in diverse plants, has been shown to inhibit tubulin formation and assembly. It binds to the colchicine site on tubulin, thereby inhibiting the growth of breast cancer cells, including multidrug resistant sublines such as MCF-7/ADR and MDA-MB-231/ADR [4]. Kokusaginine also displays modest cholinesterase inhibitory activities (IC50 = 41.46 and 70.24 µg/mL against butyrylcholinesterase and acetylcholinesterase, respectively) [5][6]. The compound has been used as a starting point to the design of antiparasitic molecules active against Trypanosoma cruzi responsible for the Chagas disease [7]. Kokusaginine is an isomer of skimmianine and a close analogue of dictamnine, both furoquinolines commonly found in Ruta species and endowed with anticancer properties [8][9][10]. There is a sound basis to investigate further the anticancer properties of kokusaginine and related furoquinoline alkaloids.
Many quinoline alkaloids have been isolated from Ruta species, such as dictamnine, pteleine, skimmianine, rutacridone, maculosidine, graveoline, graveolinine [11]. The quinolone alkaloid graveoline, initially isolated from the common rue (Ruta graveolens) [12], is a major phytotoxin from Ruta plants [13]. It is found in many Ruta, including the leaves of R. angustifolia [14][15]. In this specie, graveoline has been characterized recently as an antifungal agent inhibiting the expression of the enzyme isocitrate lyase 1 (ICL1) in the fungus Candida albicans, as observed with the reference antifungal product fluconazole [15]. However, the mechanism of action of this compound is multifactorial because it has been characterized as an inhibitor of photosynthesis [16] and as an antitumor agent capable of inducing production of reactive oxygen species (ROS) in cancer cells and triggering both apoptotic and autophagic cell death [17]. The compound is easily metabolized in the liver, with up to 12 metabolites identified [18]. The derivative graveolinine displays weaker anti-angiogenic activity than the parent compound graveoline [19] but it can serve as a starting point for the design of anti-Alzheimer agents [20]. The compound has been shown to bind to the serotonin 5-HT2B receptor and to inhibit weakly the cyclooxygenase 2 enzyme (COX2, 79% inhibition at 150 µM) [21].
A quinolin-4-one moiety is also present in arborinine, another alkaloid found in R. angustifolia. As mentioned above, this tricyclic compound can inhibit HCV replication, but it is less potent than pseudane IX [3], and it contributes to the antifungal activity of the plant extract [15]. Arborinine can be isolated from diverse plants, including Rutaceae such as Vepris trichocarpa and Vepris teva [22][23], Araliopsis soyauxii [24] and different Ruta species [25]. Interestingly, the acridone alkaloid has been shown to exert marked antitumor activities. It inhibits dose-dependently the proliferation of several cancer cell lines [26][27], triggers cell cycle arrests, blocks cancer cell migration, and induces apoptosis [28][29]. It displays a sub-micromolar activity against drug-resistant SGC-7901 gastric cancer cells resistant to adriamycin (SGC-7901/ADR: IC50 = 0.24 μM) or to vincristine (SGC-7901/VCR: IC50 = 1.09 μM) [30]. Arborinine has been characterized as a selective and reversible inhibitor of histone lysine-specific demethylase 1 (LSD1), an enzyme frequently overexpressed in cancer cells. LSD1 is a key enzyme, implicated in the epithelial-mesenchymal transition (EMT) and in tumor progression. Arborinine has the capacity to repress EMT in cancer cells, modulating the expression of specific markers (upregulation of E-cadherin, downregulation of N-cadherin and vimentin). The blockade of LSD1 with arborinine induces a dose-dependent accumulation of methylated histone H3 in cells (H3K4me1, H3K9me1, H3K9me2), thereby inducing inhibition of cancer cell migration, invasion and proliferation.
Remarkably, the compound was shown to exert a significant antitumor effect in vivo, in two xenografted murine model of gastric cancer (with SGC-7901 cells sensitive or resistant to adriamycin). At the oral dose of 40–80 mg/kg, arborinine reduced tumor growth in mice, without causing any apparent toxicity [30]. By the same token, very recently arborinine has been shown to suppress ovarian cancer development through inhibition of LSD1. The blockade of LSD1 leads to an increased expression of methylated histone H3K4m1 in SKOV3 ovarian cancer cells, thereby reducing the migration and invasion capacities of the cells due to a blocked EMT [31]. The effect is not specific to ovarian cancer cells because the LSD1 enzyme (also known as lysine (K)-specific demethylase 1A, or KDM1A) is present and frequently overexpressed in many cancer cell types. Recently, it was demonstrated that arborinine can block LSD1/KDM1A activity in clear-cell renal cell carcinoma ccRCC cell lines, sensitive or resistant to the kinase inhibitor sorafenib. In this case again, the compound blocked cell migration and invasion, cell cycle progression, and induced apoptosis [32]. A molecular modeling analysis suggested that arborinine could bind directly to the active site of LSD1, and blocks downstream signaling activities, notably the expression of the ubiquitin-conjugating enzyme E2O (UBE2O), an important protein for cancer cell survival and proliferation [32]. The observation that arborinine represses LSD1/UBE2O signaling in ccRCC opens novel perspectives for research. Firstly, in terms of drug design, it opens a field of research to discover other lysine demethylase inhibitors with an acridone or quinolin-4-one moiety. There exist many naturally-occurring analogues of arborinine, such as evoxanthine, rutacridone, quinolactacins A-C, (iso)acronycine, melicopicine and others tri/tetracyclic products. Bicyclic products derived from echinopsine shall be considered as well, notably the panel of 1-methylquinolin-4-one alkaloids such as eduline, japonine and others. Secondly, in terms of clinical applications, LSD1/KDM1A is aberrantly overexpressed in several cancer types, with different LSD1 inhibitors currently developed to treat solid tumors and hematological malignancies [33][34][35]. The antitumor activity of arborinine shall be investigated using a variety of experimental models, to define the optimal conditions and the most suitable applications in humans. Thirdly, outside oncology, LSD1/KDM1A is an enzyme of interest to treat pathologies such as myelofibrosis [36], autism [37] and other diseases [38]. The targeting of LSD1 with arborinine may have broad therapeutic implications; recently, Merck paid US$1.35 billion for LSD1 inhibitors [39]. Parenthetically, another mechanism of action has been evoked with arborinine: the binding to heme leading to a reduction of oxidative stress and inflammation [40]. However, the heme binding affinity is weak (Ka = 3.9 × 104 M−1) compared to the level of LSD1 inhibition. Nevertheless, arborinine exhibits anti-inflammatory activities. It is able to reduce the production of nitric oxide (NO) in activated macrophages [41].

2. Furocoumarins

Rutamarin is an anticancer furocoumarin derivative isolated from R. angustifolia Pers. [42] and other Ruta species [43]. The compound is moderately cytotoxic to colorectal adenocarcinoma HT29 cells (IC50 = 5.6 μM), and induces cell cycle perturbations and caspase-dependent apoptosis [43]. At the molecular level, rutamarin is believed to function as a catalytic inhibitor of human topoisomerase II (not a classical Topo II poison), binding to the ATPase domain of the enzyme, thereby blocking DNA replication [44]. This mechanism accounts for both the anticancer and antiviral activities of rutamarin, and probably for its antiprotozoal activity as well [45]. Rutamarin inhibits DNA replication of Epstein-Barr virus (EBV) (IC50 = 7.0 μM) [46][47] and Kaposi’s sarcoma-associated herpesvirus (KSHV) (IC50 = 1.12 μM), at least the (+)-enantiomer [44]. Beyond TopoII, two additional targets for rutamarin have been proposed on the basis of a molecular modeling analysis: the protein tyrosine phosphatase 1B (PTP1B) and the retinoid X receptor α (RXRα). Rutamarin would be an inhibitor of PTP1B and a RXRα agonist. The molecular models have been validated experimentally. Rutamarin effectively inhibits the PTP1B enzyme (IC50 = 6.4 µM), acting as a competitive inhibitor capable of enhancing the insulin-induced translocation of the glucose transporter 4 (GLUT4) in CHO/GLUT4 cells [48].
The dihydrofuranocoumarin chalepin can be isolated from the leaves R. angustifolia Pers. together with its furanocoumarin analogue chalepensin [49]. They are present in different Rutaceae plants [50]. They bear a 3-prenyl side chain, as in rutamarin. Chalepin displays a moderate antibacterial activity against B. substilis (Gram positive) [51] and a weak antiparasitic activity against Trypanosoma cruzi, the pathogen responsible for the Chagas disease. Chalepin and related coumarins can bind to the active site of T. cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) [52][53][54]. However, the binding affinity is weak and no anti-trypanosomal activity has been reported. Chalepin is better known for its anticancer properties. The compound displays antiproliferative activities, notably toward A549 lung cancer cells (IC50 = 27.6 μM), and triggers apoptosis with specific alterations of mitochondrial activities [49]. For a long time, the compound is known to reduce mitochondrial respiration, acting as a rotenone-like inhibitor of mitochondrial complex I [55]. It inhibits markedly the pyruvate/malate-supported proton flux in rat liver mitochondria (but is about 10 times less potent than rotenone) [56]. In cancer cells, chalepin not only alters mitochondria but affects also cell cycle progression and triggers extrinsic apoptosis [57][58].
A few other coumarins have been isolated from the aerial parts of R. angustifolia, such as 6,7,8-trimethoxycoumarin and scoparone [59]. The latter is a well-known antioxidant and lipid-lowering agent, considered useful to alleviate alcohol- or high-fat diet-induced liver injuries [60][61]. It has osteogenic effects, potentially useful to avoid bone demineralization [62], and displays antiproliferative effects against tumor cells [63]. Perhaps the most emblematic (but also confusing) coumarin is angustifolin, present in a very small amount of the aerial part of R. angustifolia [59]. The name angustifolin of the product is emblematic because it derives directly from Angustifolia, but it is confusing because the same name has been given to a totally different product, an ent-kaurane diterpenoid isolated from the aerial parts of Isodon species [64][65]. There are also four lignans named angustifolin A-D isolated from Kadsura angustifolia [66], and an alkaloid designated angustifoline (with a “e” at the end to respect the alkaloid terminology) found in Lupinus species [67][68]. Hence, the possible confusion between names Angustifolin from Ruta has been rarely cited, but it cannot be ignored [59].
Bergapten (5-methoxypsoralen) is a furocoumarin found in many plant species (notably bergamot), including R. angustifolia [49]. It is a classical antioxidant and anti-inflammatory compound, well known for its hypo-lipidemic, anti-ulcer and antidiarrheal activities [69][70]. It is also considered for the treatment of ischemic stroke [71][72]. Its known phototoxicity can be an issue, but the photoactivation could be exploited to treat skin cancers [73]. Bergapten displays anticancer properties, notably as a metabolic modulator for breast and colon cancer cells [74][75].

3. Other Compounds

A relatively rare series is called moskachans A-D, four benzodioxone derivatives, discovered initially from the aerial part of R. angustifolia [76] and later found in R. chalepensis [77]. The name moskachan comes from ‘moskatxa’, the Basque name for R. angustifolia [76] but also used for other Ruta species. Moskachan B is not cytotoxic whereas moskachan D displays a weak antiproliferative activity against A549 lung cancer cells (IC50 = 74.4 μM) [49]. In addition to these four moskachans, other compounds with a methylenedioxyphenyl moiety have been identified from an essential oil of R. angustifolia (from a specimen collected in Malaysia), including compounds structurally close to safrol which is a well-known phenylpropene derivative [78]. Moskachans have been occasionally found in other species but rarely studied. They could be further considered as ingredients in the food or perfumery industry, as it is the case for other compounds with a methylenedioxyphenyl moiety.

References

  1. Vasudevan, T.N.; Luckner, M. Alkaloids from Ruta angustifolia Pers., Ruta chalepensis L., Ruta graveolens L. and Ruta montana Mill. Pharmazie 1968, 23, 520–521.
  2. Adamska-Szewczyk, A.; Glowniak, K.; Baj, T. Furochinoline alkaloids in plants from Rutaceae family—A review. Curr. Issues Pharm. Med. Sci. 2016, 29, 33–38.
  3. Wahyuni, T.S.; Widyawaruyanti, A.; Lusida, M.I.; Fuad, A.; Soetjipto; Fuchino, H.; Kawahara, N.; Hayashi, Y.; Aoki, C.; Hotta, H. Inhibition of hepatitis C virus replication by chalepin and pseudane IX isolated from Ruta angustifolia leaves. Fitoterapia 2014, 99, 276–283.
  4. Chen, H.; Li, S.; Wang, S.; Li, W.; Bao, N.; Ai, W. The inhibitory effect of kokusaginine on the growth of human breast cancer cells and MDR-resistant cells is mediated by the inhibition of tubulin assembly. Bioorg. Med. Chem. Lett. 2018, 28, 2490–2492.
  5. Sichaem, J.; Rojpitikul, T.; Sawasdee, P.; Lugsannangarm, K.; Santi, T.P. Furoquinoline Alkaloids from the Leaves of Evodia lepta as Potential Cholinesterase Inhibitors and their Molecular Docking. Nat. Prod. Commun. 2015, 10, 1359–1362.
  6. Senol Deniz, F.S.; Eren, G.; Orhan, I.E.; Sener, B.; Ozgen, U.; Aldaba, R.; Calis, I. Outlining In Vitro and In Silico Cholinesterase Inhibitory Activity of Twenty-Four Natural Products of Various Chemical Classes: Smilagenin, Kokusaginine, and Methyl Rosmarinate as Emboldening Inhibitors. Molecules 2021, 26, 2024.
  7. Belén Valdez, M.; Bernal Giménez, D.M.; Fernández, L.R.; Musikant, A.D.; Ferri, G.; Sáenz, D.; Di Venosa, G.; Casas, A.; Avigliano, E.; Edreira, M.M.; et al. Antiparasitic Derivatives of the Furoquinoline Alkaloids Kokusaginine And Flindersiamine. ChemMedChem 2022, 17, e202100784.
  8. Zuo, Y.; Pu, J.; Chen, G.; Shen, W.; Wang, B. Study on the activity and mechanism of skimmianine against human non-small cell lung cancer. Nat. Prod. Res. 2019, 33, 759–762.
  9. Liu, Y.; Kang, L.; Shi, S.M.; Li, B.J.; Zhang, Y.; Zhang, X.Z.; Guo, X.W.; Fu, G.; Zheng, G.N.; Hao, H.; et al. Skimmianine as a novel therapeutic agent suppresses proliferation and migration of human esophageal squamous cell carcinoma via blocking the activation of ERK1/2. Neoplasma 2022, 69, 571–582.
  10. Zhang, Z.Q.; Xuan, W.L.; Huang, Y.; Ren, S.; Wulan, T.Y.; Song, Y.; Xue, D.B.; Zhang, W.H. Dictamnine inhibits pancreatic cancer cell growth and epithelial-mesenchymal transition by blocking the PI3K/AKT signaling pathway. Neoplasma 2022, 69, 603–619.
  11. El Sayed, K.; Al-Said, M.S.; El-Feraly, F.S.; Ross, S.A. New quinoline alkaloids from Ruta chalepensis. J. Nat. Prod. 2000, 63, 995–997.
  12. Shahrajabian, M.H. A Candidate for Health Promotion, Disease Prevention and Treatment, Common Rue (Ruta graveolens L.), an Important Medicinal plant in Traditional Medicine. Curr. Rev. Clin. Exp. Pharmacol. 2022; online ahead of print.
  13. Hale, A.L.; Meepagala, K.M.; Oliva, A.; Aliotta, G.; Duke, S.O. Phytotoxins from the leaves of Ruta graveolens. J. Agric. Food Chem. 2004, 52, 3345–3349.
  14. Kamal, L.Z.M.; Hassan, N.M.; Taib, N.M.; Soe, M. Graveoline from Ruta angustifolia (L.) Pers. and Its Antimicrobial Synergistic Potential in Erythromycin or Vancomycin Combinations. Sains Malays. 2018, 47, 2429–2435.
  15. Kamal, L.Z.M.; Adam, M.A.A.; Shahpudin, S.N.M.; Shuib, A.N.; Sandai, R.; Hassan, N.M.; Tabana, Y.; Basri, D.F.; Than, L.T.L.; Sandai, D. Identification of Alkaloid Compounds Arborinine and Graveoline from Ruta angustifolia (L.) Pers for their Antifungal Potential against Isocitrate lyase (ICL1) gene of Candida albicans. Mycopathologia 2021, 186, 221–236.
  16. Sampaio, O.M.; Vieira, L.C.C.; Bellete, B.S.; King-Diaz, B.; Lotina-Hennsen, B.; da Silva, M.F.D.G.F.; Veiga, T.A.M. Evaluation of Alkaloids Isolated from Ruta graveolens as Photosynthesis Inhibitors. Molecules 2018, 23, 2693.
  17. Ghosh, S.; Bishayee, K.; Khuda-Bukhsh, A.R. Graveoline isolated from ethanolic extract of Ruta graveolens triggers apoptosis and autophagy in skin melanoma cells: A novel apoptosis-independent autophagic signaling pathway. Phytother. Res. 2014, 28, 1153–1162.
  18. Liu, H.; Guo, S.; Xi, S. A high-resolution accurate mass approach to identification of graveoline metabolites using ultra-high-performance liquid chromatography combined with a photo diode array detector and quadrupole/time-of-flight tandem mass spectrometry. Biomed. Chromatogr. 2022, 37, e5511.
  19. An, Z.Y.; Yan, Y.Y.; Peng, D.; Ou, T.M.; Tan, J.H.; Huang, S.L.; An, L.K.; Gu, L.Q.; Huang, Z.S. Synthesis and evaluation of graveoline and graveolinine derivatives with potent anti-angiogenesis activities. Eur. J. Med. Chem. 2010, 45, 3895–3903.
  20. Luo, W.; Lv, J.W.; Wang, T.; Zhang, Z.Y.; Guo, H.Y.; Song, Z.Y.; Wang, C.J.; Ma, J.; Chen, Y.P. Synthesis, in vitro and in vivo biological evaluation of novel graveolinine derivatives as potential anti-Alzheimer agents. Bioorg. Med. Chem. 2020, 28, 115190.
  21. Rodrigues, T.; Reker, D.; Kunze, J.; Schneider, P.; Schneider, G. Revealing the Macromolecular Targets of Fragment-Like Natural Products. Angew. Chem. Int. Ed. Engl. 2015, 54, 10516–10520.
  22. Ombito, J.O.; Chi, G.F.; Wansi, J.D. Ethnomedicinal uses, phytochemistry, and pharmacology of the genus Vepris (Rutaceae): A review. J. Ethnopharmacol. 2021, 267, 113622.
  23. Langat, M.K.; Kami, T.; Cheek, M. Chemistry, taxonomy and ecology of the potentially chimpanzee-dispersed Vepris teva sp.nov. (Rutaceae) endangered in coastal thicket in the Congo Republic. PeerJ 2022, 10, e13926.
  24. Noulala, C.G.T.; Ouete, J.L.N.; Atangana, A.F.; Mbahbou, G.T.B.; Fotso, G.W.; Stammler, H.G.; Lenta, B.N.; Happi, E.N.; Sewald, N.; Ngadjui, B.T. Soyauxinine, a New Indolopyridoquinazoline Alkaloid from the Stem Bark of Araliopsis soyauxii Engl. (Rutaceae). Molecules 2022, 27, 1104.
  25. Al-Majmaie, S.; Nahar, L.; Rahman, M.M.; Nath, S.; Saha, P.; Talukdar, A.D.; Sharples, G.P.; Sarker, S.D. Anti-MRSA Constituents from Ruta chalepensis (Rutaceae) Grown in Iraq, and In Silico Studies on Two of Most Active Compounds, Chalepensin and 6-Hydroxy-rutin 3′,7-Dimethyl ether. Molecules 2021, 26, 1114.
  26. Réthy, B.; Zupkó, I.; Minorics, R.; Hohmann, J.; Ocsovszki, I.; Falkay, G. Investigation of cytotoxic activity on human cancer cell lines of arborinine and furanoacridones isolated from Ruta graveolens. Planta Med. 2007, 73, 41–48.
  27. Réthy, B.; Hohmann, J.; Minorics, R.; Varga, A.; Ocsovszki, I.; Molnár, J.; Juhász, K.; Falkay, G.; Zupkó, I. Antitumour properties of acridone alkaloids on a murine lymphoma cell line. Anticancer Res. 2008, 28, 2737–2743.
  28. Kuete, V.; Sandjo, L.P.; Seukep, J.A.; Zeino, M.; Mbaveng, A.T.; Ngadjui, B.; Efferth, T. Cytotoxic compounds from the fruits of Uapaca togoensis towards multifactorial drug-resistant cancer cells. Planta Med. 2015, 81, 32–38.
  29. Piboonprai, K.; Khumkhrong, P.; Khongkow, M.; Yata, T.; Ruangrungsi, N.; Chansriniyom, C.; Iempridee, T. Anticancer activity of arborinine from Glycosmis parva leaf extract in human cervical cancer cells. Biochem. Biophys. Res. Commun. 2018, 500, 866–872.
  30. Chu, Y.; Xiao, Z.; Jing, N.; Yan, W.; Wang, S.; Ma, B.; Zhang, J.; Li, Y. Arborinine, a potential LSD1 inhibitor, inhibits epithelial-mesenchymal transition of SGC-7901 cells and adriamycin-resistant gastric cancer SGC-7901/ADR cells. Investig. New Drugs 2021, 39, 627–635.
  31. Li, N.; Yang, L.; Zuo, H. Arborinine suppresses ovarian cancer development through inhibition of LSD1. Life Sci. 2022, 291, 120275.
  32. Feng, C.; Gong, L.; Wang, J. Arborinine from Glycosmis parva leaf extract inhibits clear-cell renal cell carcinoma by inhibiting KDM1A/UBE2O signaling. Food Nutr. Res. 2022, 66, 1–8.
  33. Mehndiratta, S.; Liou, J.P. Histone lysine specific demethylase 1 inhibitors. RSC Med. Chem. 2020, 11, 969–981.
  34. Zhang, X.; Wang, X.; Wu, T.; Yin, W.; Yan, J.; Sun, Y.; Zhao, D. Therapeutic potential of targeting LSD1/ KDM1A in cancers. Pharmacol. Res. 2022, 175, 105958.
  35. Zheng, Y.C.; Liu, Y.J.; Gao, Y.; Wang, B.; Liu, H.M. An Update of Lysine Specific Demethylase 1 Inhibitor: A Patent Review (2016–2020). Recent Pat. Anticancer Drug Discov. 2022, 17, 9–25.
  36. Gill, H. Lysine-Specific Demethylase 1 (LSD1/KDM1A) Inhibition as a Target for Disease Modification in Myelofibrosis. Cells 2022, 11, 2107.
  37. Rapanelli, M.; Williams, J.B.; Ma, K.; Yang, F.; Zhong, P.; Patel, R.; Kumar, M.; Qin, L.; Rein, B.; Wang, Z.J.; et al. Targeting histone demethylase LSD1 for treatment of deficits in autism mouse models. Mol. Psychiatry 2022, 27, 3355–3366.
  38. Maiques-Diaz, A.; Somervaille, T.C. LSD1: Biologic roles and therapeutic targeting. Epigenomics 2016, 8, 1103–1116.
  39. Mullard, A. Merck & Co. pays US$1.35 billion for LSD1 inhibitors. Nat. Rev. Drug Discov. 2022; online ahead of print.
  40. Pal, C.; Kundu, M.K.; Bandyopadhyay, U.; Adhikari, S. Synthesis of novel heme-interacting acridone derivatives to prevent free heme-mediated protein oxidation and degradation. Bioorg. Med. Chem. Lett. 2011, 21, 3563–3567.
  41. Laprasert, C.; Chansriniyom, C.; Limpanasithikul, W. S-deoxydihydroglyparvin from Glycosmis parva inhibits lipopolysaccharide induced murine macrophage activation through inactivating p38 mitogen activated protein kinase. J. Adv. Pharm. Technol. Res. 2021, 12, 32–39.
  42. Suhaimi, S.A.; Hong, S.L.; Abdul Malek, S.N. Rutamarin, an Active Constituent from Ruta angustifolia Pers., Induced Apoptotic Cell Death in the HT29 Colon Adenocarcinoma Cell Line. Pharmacogn. Mag. 2017, 13, S179–S188.
  43. Kozioł, E.; Luca, S.V.; Ağalar, H.G.; Sağlık, B.N.; Demirci, F.; Marcourt, L.; Wolfender, J.L.; Jóźwiak, K.; Skalicka-Woźniak, K. Rutamarin: Efficient Liquid-Liquid Chromatographic Isolation from Ruta graveolens L. and Evaluation of Its In Vitro and In Silico MAO-B Inhibitory Activity. Molecules 2020, 25, 2678.
  44. Xu, B.; Wang, L.; González-Molleda, L.; Wang, Y.; Xu, J.; Yuan, Y. Antiviral activity of (+)-rutamarin against Kaposi’s sarcoma-associated herpesvirus by inhibition of the catalytic activity of human topoisomerase II. Antimicrob. Agents Chemother. 2014, 58, 563–573.
  45. Bazaldúa-Rodríguez, A.F.; Quintanilla-Licea, R.; Verde-Star, M.J.; Hernández-García, M.E.; Vargas-Villarreal, J.; Garza-González, J.N. Furanocoumarins from Ruta chalepensis with Amebicide Activity. Molecules 2021, 26, 3684.
  46. Wu, T.; Wang, Y.; Yuan, Y. Antiviral activity of topoisomerase II catalytic inhibitors against Epstein-Barr virus. Antiviral Res. 2014, 107, 95–101.
  47. Lin, Y.; Wang, Q.; Gu, Q.; Zhang, H.; Jiang, C.; Hu, J.; Wang, Y.; Yan, Y.; Xu, J. Semisynthesis of (-)-Rutamarin Derivatives and Their Inhibitory Activity on Epstein-Barr Virus Lytic Replication. J. Nat. Prod. 2017, 80, 53–60.
  48. Zhang, Y.; Zhang, H.; Yao, X.G.; Shen, H.; Chen, J.; Li, C.; Chen, L.; Zheng, M.; Ye, J.; Hu, L.; et al. (+)-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice. PLoS ONE 2012, 7, e31811.
  49. Richardson, J.S.; Sethi, G.; Lee, G.S.; Malek, S.N. Chalepin: Isolated from Ruta angustifolia L. Pers induces mitochondrial mediated apoptosis in lung carcinoma cells. BMC Complement. Altern. Med. 2016, 16, 389.
  50. Nahar, L.; El-Seedi, H.R.; Khalifa, S.A.M.; Mohammadhosseini, M.; Sarker, S.D. Ruta Essential Oils: Composition and Bioactivities. Molecules 2021, 26, 4766.
  51. Tamene, D.; Endale, M. Antibacterial Activity of Coumarins and Carbazole Alkaloid from Roots of Clausena anisata. Adv. Pharmacol. Sci. 2019, 2019, 5419854.
  52. Pavão, F.; Castilho, M.S.; Pupo, M.T.; Dias, R.L.; Correa, A.G.; Fernandes, J.B.; da Silva, M.F.; Mafezoli, J.; Vieira, P.C.; Oliva, G. Structure of Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase complexed with chalepin, a natural product inhibitor, at 1.95 A resolution. FEBS Lett. 2002, 520, 13–17.
  53. Menezes, I.R.; Lopes, J.C.; Montanari, C.A.; Oliva, G.; Pavão, F.; Castilho, M.S.; Vieira, P.C.; Pupo, M.T. 3D QSAR studies on binding affinities of coumarin natural products for glycosomal GAPDH of Trypanosoma cruzi. J. Comput. Aided Mol. Des. 2003, 17, 277–290.
  54. de Marchi, A.A.; Castilho, M.S.; Nascimento, P.G.; Archanjo, F.C.; del Ponte, G.; Oliva, G.; Pupo, M.T. New 3-piperonylcoumarins as inhibitors of glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) from Trypanosoma cruzi. Bioorg. Med. Chem. 2004, 12, 4823–4833.
  55. Olorunsogo, O.O.; Emerole, G.O.; Malomo, S.O.; Thabrew, M.I. Inhibition of mitochondrial respiration by chalepin, a naturally occurring furocoumarin. Toxicol. Lett. 1983, 15, 323–327.
  56. Olorunsogo, O.O.; Uwaifo, A.O.; Malomo, S.O. Comparative effects of three naturally occurring furanocoumarins on mitochondrial bioenergetics. Chem. Biol. Interact. 1990, 74, 263–274.
  57. Richardson, J.S.M.; Aminudin, N.; Abd Malek, S.N. Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549). Pharmacogn. Mag. 2017, 13, S489–S498.
  58. Fakai, M.I.; Abd Malek, S.N.; Karsani, S.A. Induction of apoptosis by chalepin through phosphatidylserine externalisations and DNA fragmentation in breast cancer cells (MCF7). Life Sci. 2019, 220, 186–193.
  59. Del Castillo, J.B.; Luis, F.R.; Secundino, M. Angustifolin, a coumarin from Ruta angustifolia. Phytochemistry 1984, 23, 2095–2096.
  60. Jiang, Y.; Xu, J.; Huang, P.; Yang, L.; Liu, Y.; Li, Y.; Wang, J.; Song, H.; Zheng, P. Scoparone Improves Nonalcoholic Steatohepatitis Through Alleviating JNK/Sab Signaling Pathway-Mediated Mitochondrial Dysfunction. Front. Pharmacol. 2022, 13, 863756.
  61. Wei, M.; Li, T.; Cao, H.; He, H.; Yang, C.; Yin, Y.; Lu, H.; Novák, P.; Zhang, K.; Gao, Y. The effects of scoparone on alcohol and high-fat diet-induced liver injury revealed by RNA sequencing. Biomed. Pharmacother. 2022, 155, 113770.
  62. Park, K.R.; Kim, B.; Lee, J.Y.; Moon, H.J.; Kwon, I.K.; Yun, H.M. Effects of Scoparone on differentiation, adhesion, migration, autophagy and mineralization through the osteogenic signalling pathways. J. Cell. Mol. Med. 2022, 26, 4520–4529.
  63. Li, N.; Yang, F.; Liu, D.Y.; Guo, J.T.; Ge, N.; Sun, S.Y. Scoparone inhibits pancreatic cancer through PI3K/Akt signaling pathway. World J. Gastrointest. Oncol. 2021, 13, 1164–1183.
  64. Na, Z.; Xiang, W.; Niu, X.M.; Mei, S.X.; Lin, Z.W.; Li, C.M.; Sun, H.D. Diterpenoids from Isodon enanderianus. Phytochemistry 2002, 60, 55–60.
  65. Han, Q.B.; Zhao, A.H.; Zhang, J.X.; Lu, Y.; Zhang, L.L.; Zheng, Q.T.; Sun, H.D. Cytotoxic constituents of Isodon rubescens var. lushiensis. J. Nat. Prod. 2003, 66, 1391–1394.
  66. Chen, Y.G.; Qin, G.W.; Xie, Y.Y.; Cheng, K.F.; Lin, Z.W.; Sun, H.D.; Kang, Y.H.; Han, B.H. Lignans from Kadsura angustifolia. J. Asian Nat. Prod. Res. 1998, 1, 125–131.
  67. Wysocka, W.; Przybyt, A. (+)-Angustifoline: A Minor Alkaloid from Lupinus albus1. Planta Med. 1993, 59, 289.
  68. Cely-Veloza, W.; Quiroga, D.; Coy-Barrera, E. Quinolizidine-Based Variations and Antifungal Activity of Eight Lupinus Species Grown under Greenhouse Conditions. Molecules 2022, 27, 305.
  69. Aslam, H.; Khan, A.U.; Qazi, N.G.; Ali, F.; Hassan, S.S.U.; Bungau, S. Pharmacological basis of bergapten in gastrointestinal diseases focusing on H+/K+ ATPase and voltage-gated calcium channel inhibition: A toxicological evaluation on vital organs. Front. Pharmacol. 2022, 13, 1005154.
  70. Quetglas-Llabrés, M.M.; Quispe, C.; Herrera-Bravo, J.; Catarino, M.D.; Pereira, O.R.; Cardoso, S.M.; Dua, K.; Chellappan, D.K.; Pabreja, K.; Satija, S.; et al. Pharmacological Properties of Bergapten: Mechanistic and Therapeutic Aspects. Oxid. Med. Cell Longev. 2022, 2022, 8615242.
  71. Gao, S.; Zou, X.; Wang, Z.; Shu, X.; Cao, X.; Xia, S.; Shao, P.; Bao, X.; Yang, H.; Xu, Y.; et al. Bergapten attenuates microglia-mediated neuroinflammation and ischemic brain injury by targeting Kv1.3 and Carbonyl reductase 1. Eur. J. Pharmacol. 2022, 933, 175242.
  72. Yang, Y.; Han, J.; Lilly, R.G.; Yang, Q.; Guo, Y. Bergapten mediated inflammatory and apoptosis through AMPK/eNOS/AKT signaling pathway of isoproterenol-induced myocardial infarction in Wistar rats. J. Biochem. Mol. Toxicol. 2022, 36, e23143.
  73. Liang, Y.; Xie, L.; Liu, K.; Cao, Y.; Dai, X.; Wang, X.; Lu, J.; Zhang, X.; Li, X. Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity. Phytother. Res. 2021, 35, 6131–6147.
  74. Santoro, M.; Guido, C.; De Amicis, F.; Sisci, D.; Cione, E.; Vincenza, D.; Donà, A.; Panno, M.L.; Aquila, S. Bergapten induces metabolic reprogramming in breast cancer cells. Oncol. Rep. 2016, 35, 568–576.
  75. Lin, C.P.; Lin, C.S.; Lin, H.H.; Li, K.T.; Kao, S.H.; Tsao, S.M. Bergapten induces G1 arrest and pro-apoptotic cascade in colorectal cancer cells associating with p53/p21/PTEN axis. Environ. Toxicol. 2019, 34, 303–311.
  76. Del Castillo, J.B.; Secundino, M.; Luis, F.R. Four aromatic derivatives from Ruta angustifolia. Phytochemistry 1986, 25, 2209–2210.
  77. Ulubelen, A.; Tan, N. A moskachan from roots of Ruta chalepensis. Phytochemistry 1990, 29, 3991–3992.
  78. Joulain, D.; Laurent, R.; Fourniol, J.P.; Yaacob, K.B. Novel Moskachan Related Compounds in the Essential Oil of Ruta angustifolia Pers. from Malaysia. J. Essential Oil Res. 1991, 3, 355–357.
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