Plantago major has long been used for medical purposes in Indonesia. However, reports on the anti-arthritic activities of P. major are limited. The anti-arthritic properties of an n-hexane-insoluble fraction of dichloromethane extracts of P. major (IPM) were evaluated using Complete Freund's Adjuvant (CFA)-induced arthritis induced in female Wistar rat by CFA. Diclofenac was used as a positive control. The volume of paw oedema, white blood cell count, lymphocytes, neutrophils, expression of TNF-α and Interleukin-6 and the histopathological features of the joint tissues were assessed to characterise IPM activity. The IPM extract at doses of 280 and 420 mg/kg BW and diclofenac inhibited paw oedema by 15.70 %, 15.94 % and 19.71 % respectively. IPM also reduced the incidence of arthritis and arthritic index. Unlike untreated rats, animals treated with IPM showed a significant decrease in the number of neutrophils and decreased expression of TNF-α and Interleukin-6. Histopathological examination showed a reduction in the number of inflammatory cells and hyperplasia of the synovium after IPM treatment. This study showed that P. major displays anti-rheumatoid arthritis activity.

Microbial interactions between filamentous fungi and yeast are still not fully understood. To evaluate a potential antifungal activity of a filamentous fungus while highlighting metabolomic changes, co-cultures between an endophytic strain of Cophinforma mamane (CM) and Candida albicans (CA) were performed. The liquid cultures were incubated under static conditions and metabolite alterations during the course were investigated by ultra-performance liquid chromatography–tandem mass spectrophotometry (UPLC–MS/MS). Results were analyzed using MS-DIAL, MS-FINDER, METLIN, Xcalibur, SciFinder, and MetaboAnalyst metabolomics platforms. The metabolites associated with catabolic processes, including the metabolism of branched-chain amino acids, carnitine, and phospholipids were upregulated both in the mono and co-cultures, indicating fungal adaptability to environmental stress. Several metabolites, including C20 sphinganine 1-phosphate, myo-inositol, farnesol, gamma-undecalactone, folinic acid, palmitoleic acid, and MG (12:/0:0/0:0) were not produced by CA during co-culture with CM, demonstrating the antifungal mechanism of CM. Our results highlight the crucial roles of metabolomics studies to provide essential information regarding the antifungal mechanism of C. mamane against C. albicans, especially when the lost/undetected metabolites are involved in fungal survival and pathogenicity. Graphical Abstract

Background: Phyllanthus niruri (meniran) is a medicinal plant with antimicrobial, antioxidant, anticancer, anti-inflammatory, antiplasmodial, antiviral, hepatoprotective diuretic, and immunomodulator properties. Objective: This review examined the activity, mode of action, and active compounds of P. niruri as an immunomodulator in various preclinical and clinical studies, along with the bioactive compounds and their mechanism. Results: Flavonoids, lignans, terpenoids, and alkaloids, among other phytochemicals found in P. niruri, play an essential part in the pharmacological activity of the plant. The immunomodulation activity of P. niruri has been extensively researched in preclinical (in silico, in vitro, and in vivo) and clinical trials. A study in silico revealed the potential of P. niruri as an immunomodulator in Covid-19 infection by inhibiting the COVID-19 target receptors spike glycoprotein (6LZG) and major protease (5R7Y and Mpro). In addition, P. niruri boosted macrophage phagocytic activity, increased antibody total, and reduced inflammation in vitro and in vivo experiments. P. niruri also showed immunomodulatory effects in both healthy subjects and patients. Conclusion: P. niruri exhibits pharmacological potential as an immunomodulator in preclinical and clinical trials, according to the findings of various investigations. Keywords: Phyllanthus niruri, immunomodulator, immunostimulant Intisari  Latar belakang: Phyllanthus niruri merupakan tanaman obat yang memiliki beberapa aktivitas farmakologi seperti antimikroba, antioksidan, antikanker, antiinflamasi, antiplasmodium, antivirus, diuretik, hepatoprotektif, dan sebagai imunomodulator. Tujuan: Melakukan tinjauan analisis mengenai aktivitas, mekanisme, dan senyawa aktif P. niruri sebagai imunomodulator pada uji preklinis maupun uji klinis. Hasil: Kandungan kimia P. niruri seperti flavonoid, lignan, terpenoid, dan alkaloid berperan penting pada aktivitas farmakologi P. niruri sebagai imunomodulator. Uji in silico menunjukkan potensi P. niruri sebagai imunomodulator pada infeksi Covid-19 dengan berikatan pada protein spike dan protease yang bertanggungjawab pada replikasi dan pematangan virus. Uji in vitro dan in vivo menunjukkan bahwa P. niruri mampu meningkatkan aktivitas fagositosis dari makrofag, meningkatkan antibodi serum total, dan mengurangi inflamasi. Pengujian klinis membuktikan bahwa P. niruri memiliki aktivitas imunomodulator baik pada subjek uji sehat maupun pada pasien. Kesimpulan: P. niruri memiliki aktivitas sebagai imunomodulator baik pada pengujian preklinis maupun klinis. Kata kunci : P. niruri, imunomodulator, imunostimulan