Immunomodulatory Constituents Research Articles

Exploration of the Synergistic Effects of Phytoconstituents of Ashwagandha, Amla, and Ginger as a Potent Immunity-Boosting Agent for Covid-19 Affected Individuals

Abstract: The ongoing threat of COVID-19 has prompted us to search for innovative strategies to enhance immune responses in affected patients. Phytoconstituents derived from Ashwagandha, Amla, and Ginger have gained attention due to their historical usage in traditional medicine and potential immune-modulatory, antioxidant, and antiviral properties. This review investigates the synergistic effects of phytoconstituents from Ashwagandha, Amla, and Ginger to identify potential immunity-boosting agents for COVID-19 patients. The investigation involved a comprehensive analysis of the immune-modulatory compounds present in Ashwagandha, the high vitamin C content in Amla, and the immunomodulatory constituents in Ginger. The concept of "phytochemical synergy" was explored, hypothesizing that their combined effects could enhance antiviral capabilities. The combined phytoconstituents from Ashwagandha, Amla, and Ginger demonstrated a potential synergistic interaction, suggesting an amplified immune-boosting effect. The adaptogenic properties of Ashwagandha, the rich vitamin C source in Amla, and the immunomodulatory components of Ginger appeared to complement each other, contributing to a holistic approach to viral resistance. While the investigation into the synergy of Ashwagandha, Amla, and Ginger holds promise as an immunity-boosting strategy, careful consideration is warranted due to factors like appropriate dosing, safety profiles, and potential interactions with conventional treatments. This study underscores the significance of combining traditional wisdom with modern research efforts. As the world continues to combat the complexities of COVID-19, exploring these botanical sources serves as a reminder of the abundant resources nature offers. While further rigorous research and clinical trials are essential, pursuing these phytoconstituents exemplifies our commitment to exploring all viable avenues in the battle against COVID-19.

Network pharmacology to uncover potential anti-inflammatory and immunomodulatory constituents in Curcuma longa rhizome as complementary treatment in COVID-19

The immune status of patients plays an essential role in COVID-19. Herbal medicine with immunomodulatory and anti-inflammatory effect could have potential as a complementary therapeutic along with modern medicine. This study aims to investigate the anti-inflammatory and immunomodulatory constituents of Curcuma longa (C. longa) and its possible mechanisms in COVID-19. We systematically sorted the biochemical of C. longa rhizome from literature and repository. Next, we investigated targets related to COVID-19 in the selected active phytochemical constituents and analyzed the possible mechanisms against COVID-19 and performed molecular docking with four essential target proteins in COVID-19 for further verification. Ten active phytochemical constituents of C. longa were predicted to interact with four protein targets. The epidermal growth factor was the most interacted protein targeted by Calebin A, curcumin, cyclocurcumin, demethoxycurcumin, turmeronol a, turmeronol b, caffeic acid, and quercetin. Interferon-gamma was performed as the most critical protein targeted by 4-hydroxycinnamic acid. Curcumin was also predicted to interact with toll-like receptor 4 and Ar-turmerone with angiotensin II receptor type 2. We also reported four signaling pathways associated with target proteins-active phytochemical constituents against COVID-19: cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, Jak-STAT signaling pathway, and PI3K-Akt signaling pathway. In conclusion, multi compounds in C. longa might act synergistically against COVID-19 by affecting the inflammatory and immune responses, and other pathological processes through multiple targets and pathways.

Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects.

Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant’s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors.

Immunomodulatory Constituents of Human Donor Milk.

Mother's own human milk is the best nutrition for infants, especially preterm very-low-birth-weight (VLBW) (≤1,500 g) infants, because of its immune-modulatory constituents that strengthen the infant's host defense, provide protection against infections, and decrease the risk of necrotizing enterocolitis (NEC). When mother's own milk is unavailable or insufficient, donor human milk is considered the best alternative, especially for preterm VLBW infants. However, to assure biological safety, donor milk must be pasteurized. This results in partial or complete inactivation of some of the immunomodulatory constituents of human milk, which confer host defense. This review summarizes the current evidence regarding the effects of pasteurization on the different immunological constituents of donor milk, and their clinical significance, especially in relation to prevention of NEC.

POM analyses, immunomodulatory, cytotoxic activities and polyphenolic constituents of Callistemon viridiflorus fruits

Phytochemical study on 80% ethanolic extract of Callistemon viridiflorus Sims fruits (CVF) resulted in isolation of five phenolic compounds 1; Gallic acid, 2; Ellagic acid, 3; Reynoutrin, 4; Methoxy ellagic acid, 5; Quercetin. Petra/Osiris/Molinspiration (POM) analyses predicted that Reynoutrin and Quercetin have interesting potential activities, also Reynoutrin is found to be safer in relation to Quercetin. 80% ethanolic extract of CVF, Reynoutrin and Quercetin displayed remarkable immunomodulatory activity, as increased proliferation of RAW 264.7 macrophage cells by 1.48, 1.51 and 1.46 fold respectively. 80% ethanolic extract of the C. viridiflorus fruits showed significant cytotoxic activity against P388 leukemia cells (IC50 = 15.11 µg/ml), followed by Quercetin (IC50 = 21.5 µg/ml) then Reynoutrin (IC50 = 33.32 µg/ml).

Herbal Immunomodulators - A Remedial Panacea for Designing and Developing Effective Drugs and Medicines: Current Scenario and Future Prospects.

Constant exposure to various stressors, such as immune pressure, rapidly increasing population, deleterious changes in the ecosystem, climate change, infection with emerging and re-emerging pathogens, and fast-paced lifestyle, is a critical factor in the globally increasing incidences of immunocompromising health conditions, as well as stress. Synthetic chemotherapeutic agents, which are widely available in the commercial market, may be highly efficacious, but most are immunosuppressive and exert many side effects. Herein, we comprehensively reviewed current literature from various scientific databases such as Bentham Science, PubMed, Scopus, Elsevier, Springer, etc. The inclusion/exclusion criteria based on literature with high importance was adopted to analyze and compile salient information from the authentic bibliographic sources. Undoubtedly, the pivotal characteristics of immunostimulants and immunomodulators in the maintenance of the health and productivity of humans, as well as animals, cannot be overlooked. Numerous herbs used in ethnoveterinary medicine can be successfully employed as adjuvant rehabilitators to negate the deleterious effects of chemotherapeutics. The sources of these medicinal remedies are part of long traditions in different regions of the world, such as Indian Ayurveda and Traditional Chinese Medicine, which have been developed through empirical experience. Traditional medicine employs a holistic approach to the prevention of disease, and traditional herbal medicines are a source of many components with a high therapeutic value that are used in modern allopathic medicine. Globally, many studies have been conducted on these herbs and have revealed unique active constituents that activate the innate immune system through the stimulation of macrophages and lymphocytes, and modulation of the cytokine profile, which leads to a state of alertness with a subsequent reduction in the incidence of infection. Immunomodulatory constituents with herbal origins are termed as phytochemicals, including flavonoids, glycosides, polysaccharides, terpenoids, essential oils, various bitters, and alkaloids; all these compounds exert vital, multidimensional effects. Efforts have focused on screening plant preparations to identify adjuvant immune properties; furthermore, several potent phytol adjuvants have been experimentally proven to downregulate inflammatory reactions in addition to enhance specific adaptive responses to vaccines. In summary, this review summarizes the current status and future prospects regarding the immunomodulatory potential of various herbs and plants and their promising utility for designing and developing effective drugs and medicines in safeguarding the health of humans, animals, and poultry.

Immunomodulatory constituents from Ascomycetous fungi.

Our screening project, namely, search for new immunomodulatory constituents from Ascomycetous fungi, was guided by the effects on mitogen-induced proliferations of mouse spleen lymphocytes. On the project, the defatted crude extracts from Gelasinospora multiforis, G. heterospora, G. longispora, G. kobi, Diplogelasinospora grovesii, Emericella aurantio-brunnea, Eupenicillium crustaceum, etc., submitted to the solvent partition followed by fractionation with repeated chromatography monitored by immunomodulatory activity to afford many active constituents, of which molecular structures including absolute configurations and immunomodulatory activities were elucidated. All of these immunomodulatory constituents isolated on the project were practically not immunostimulants but immunosuppressants.

Immunomodulatory constituents of human breast milk and immunity from bronchiolitis

BackgroundThe mother’s immune status can be achieved by genetic and breastfeeding impact descendants of the immune system. The study aimed to determine whether a mother’s immune status and breastfeeding practices were related to development of bronchiolitis in her infant.MethodsThe frequency of T, B and natural kill (NK) cells in patients’ blood and their mothers’ breast milk was determined using flow cytometry. The concentrations of serum and breast milk IgG and IgD in individual patients and healthy control were determined by enzyme-linked immunosorbent assay (ELISA). The relationships between immunocytes, immunoglobulin and respiratory score (RS) were analyzed by Spearman’s rank correlation test.ResultsThe mothers of bronchiolitis patients had lower IgG concentrations in their breast milk when compared to the mothers of healthy children. There was no significant difference in the frequency of T cells, B cells, and NK cells in samples of breast milk. However, significant decreases of CD3+, CD8+ T cells, as well as significant increases of CD4+ T cells and CD19+ B cells were found in the serum of bronchiolitis infants. There were positive correlation relationships between RS and CD3+, CD4+ T cells, IgG and IgD concentrations.ConclusionOur data suggested that the mothers of bronchiolitis patients had lower IgG concentration in their breast milk. The breast milk IgG might be absorbed by the breastfeeding infants, which could play important role in resistance of bronchiolitis.

Lipophilic fractions from the marine sponge Halichondria sitiens decrease secretion of pro-inflammatory cytokines by dendritic cells and decrease their ability to induce a Th1 type response by allogeneic CD4+ T cells

Context: Halichondria (Halichondriidae) marine sponges contain components possessing various biological activities, but immunomodulation is not among the ones reported.Objective: This study evaluated the immunomodulatory effects of fractions/compounds from Halichondria sitiens Schmidt.Materials and methods: Crude dichloromethane/methanol extracts of H. sitiens were subjected to various chromatographic techniques to obtain fractions/compounds with immunomodulatory activity, using bioassay-guided isolation. The effects of the fractions/compounds were determined by measuring secretion of cytokines and expression of surface molecules by dendritic cells (DCs) and their ability to stimulate and modify cytokine secretion by allogeneic CD4+ T cells. The bioactive fractions were chemically analyzed to identify the immunomodulatory constituents by 1D, 2D NMR, and HRMS data.Results: Several lipophilic fractions from H. sitiens at 10 μg/mL decreased secretion of the pro-inflammatory cytokines IL-12p40 and IL-6 by the DCs, with maximum inhibition being 64% and 25%, respectively. In addition, fractions B3b3F and B3b3J decreased the ability of DCs to induce T cell secretion of IFN-γ. Fraction B3b3 induced morphological changes in DCs, characterized by extreme elongation of dendrites and cell clustering. Chemical screening revealed the presence of glycerides and some minor unknown constituents in the biologically active fractions. One new glyceride, 2,3-dihydroxypropyl 2-methylhexadecanoate (1), was isolated from one fraction and two known compounds, 3-[(1-methoxyhexadecyl)oxy]propane-1,2-diol (2) and monoheptadecanoin (3), were identified in another, but none of them had immunomodulatory activity.Discussion and conclusions: These results demonstrate that several lipophilic fractions from H. sitiens have anti-inflammatory effects on DCs and decrease their ability to induce a Th1 type immune response.

Significance of antigen and epitope specificity in tuberculosis.

Tuberculosis (TB) remains a major global health problem, because (i) diagnosis is usually made too late to avoid spread of infection to contacts; (ii) vaccination with bacillus Calmette‐Guerin (BCG) does not prevent the most prevalent pulmonary disease; and (iii) defaulting from lengthy chemotherapy leads to an increase in drug resistant strains. The continued impact of human immunodeficiency virus (HIV) co-infections remains a major aggravating factor in TB resurgence. Intensive research on the specificity and function of immunological responses is of major importance since protective host defense is critically dependent on T cells, which selectively recognize only certain antigens and epitopes of the tubercle bacillus. Such knowledge is therefore necessary for designing a novel effective vaccine and better diagnostic tools. The specificity of the host immune response may also help to explain how the intracellular tubercle bacilli evade host resistance, probably by decoy pro-inflammatory actions of some of their antigens and/or immunomodulatory constituents, which lead to chronic infection and lung pathology. The 12 articles in this Research Topic in the section Microbial Immunology of the journal Frontiers in Immunology review current knowledge, as well as gaps in our understanding of the mechanisms and functions of T and B cell recognition of antigens and constituent epitopes of Mycobacterium tuberculosis (Mtb). The abundant occurrence of major histocompatibility complex (MHC) class II-permissive epitopes in tubercle bacilli has important implications for the development of both subunit vaccines and diagnostic tests (1, 2). Moreover, an evolutionary interpretation has been that selection of Mtb strains carrying protective MHC-permissive epitopes could have extended the survival of infectious individuals and hence was advantageous for the protracted aerosol transmission of the pathogen (1).

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

Changes in immunomodulatory constituents of human milk in response to active infection in the nursing infant

To investigate whether immunologic factors in breast milk change in response to nursing infants' infection. Total CD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. Such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. Secretory immunoglobulin A levels did not change significantly in the study or control group. During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants. Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.

Triterpene Acids from Rose Hip Powder Inhibit Self‐antigen‐ and LPS‐induced Cytokine Production and CD4+ T‐cell Proliferation in Human Mononuclear Cell Cultures

A triterpene acid mixture consisting of oleanolic, ursolic and betulinic acid isolated from a standardized rose hip powder (Rosa canina L.) has been shown to inhibit interleukin (IL)-6 release from Mono Mac 6 cells. The present study examined the effects of the triterpene acid mixture on the cytokine production and proliferation of CD4⁺ T cells and CD19⁺ B cells induced by a self-antigen, human thyroglobulin and by lipopolysaccharide in cultures of normal mononuclear cells. The triterpene acid mixture inhibited the production of tumor necrosis factor-α and IL-6 with estimated IC₅₀ values in the range 35-56 µg/mL, the Th1 cytokines interferon-γ and IL-2 (IC₅₀ values 10-20 µg/mL) and the antiinflammatory cytokine IL-10 (IC₅₀ values 18-21 µg/mL). Moreover, the mixture also inhibited CD4⁺ T-cell and CD19⁺ B-cell proliferation (IC₅₀ value 22 and 12 µg/mL, respectively). Together, these data demonstrate that oleanolic, ursolic and betulinic acid are active immunomodulatory constituents of the standardized rose hip powder. However, since the estimated IC₅₀ values are in the µg/mL range, it is questionable whether the content of the triterpene acids in the standardized rose hip powder, alone, can explain the reported clinical effects.

Lipoarabinomannan and related glycoconjugates: structure, biogenesis and role inMycobacterium tuberculosisphysiology and host–pathogen interaction

Approximately one third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of tuberculosis. This bacterium has an unusual lipid-rich cell wall containing a vast repertoire of antigens, providing a hydrophobic impermeable barrier against chemical drugs, thus representing an attractive target for vaccine and drug development. Apart from the mycolyl–arabinogalactan–peptidoglycan complex, mycobacteria possess several immunomodulatory constituents, notably lipomannan and lipoarabinomannan. The availability of whole-genome sequences of M. tuberculosis and related bacilli over the past decade has led to the identification and functional characterization of various enzymes and the potential drug targets involved in the biosynthesis of these glycoconjugates. Both lipomannan and lipoarabinomannan possess highly variable chemical structures, which interact with different receptors of the immune system during host–pathogen interactions, such as Toll-like receptors-2 and C-type lectins. Recently, the availability of mutants defective in the synthesis of these glycoconjugates in mycobacteria and the closely related bacterium, Corynebacterium glutamicum, has paved the way for host–pathogen interaction studies, as well as, providing attenuated strains of mycobacteria for the development of new vaccine candidates. This review provides a comprehensive account of the structure, biosynthesis and immunomodulatory properties of these important glycoconjugates.

Steroids and triterpenoids from Eastern Nigeria mistletoe, Loranthus micranthus Linn. (Loranthaceae) parasitic on Kola acuminata with immunomodulatory potentials

In search of immunomodulatory constituents from the Eastern Nigeria mistletoe, Loranthus micranthus Linn, two new stigmastane steroids: stigmast-7,20 (21)-diene-3β-hydroxy-6-one ( 1) and 3β-hydroxy-stigmast-23-ene ( 2); three (two new and one known) lupeol-based triterpenoid esters: 7β,15α-dihydroxyl-lup-20(29)-ene-3β-palmitate ( 3), 7β,15α-dihydroxyl-lup-20(29)-ene-3β-stearate ( 4) and 7β,15α-dihydroxyl-lup-20(29)-ene-3β-eicosanoate ( 5) were isolated and characterized following bioactivity-guided fractionation. The new compounds, 1, 2, 4 and 5 at concentrations of 10, 25 and 100 μg/ml were subjected to cell proliferation and early activation marker (CD69) expression studies in C57Bl/6 mice splenocytes using flow cytometry techniques against Lipopolysaccharide (LPS; 10 μg/ml) and Concanavalin A (ConA; 2 μg/ml) standards. The stigmastane steroids ( 1 and 2) at the highest concentration of 100 μg/ml showed statistically significantly ( p < 0.05) stimulatory activity on the C57B1/6 splenocytes compared to the controls with values of 46 ± 0.76% and 43 ± 0.46% compared to 7.69 ± 0.41% recorded for the negative control. The novel lupeol esters, 4 and 5 at same concentration of 100 μg/ml exhibited lower stimulations of 30 ± 0.41% and 29 ± 0.17% respectively compared to the controls above. The CD69 expression assay at the above doses showed that all the compounds have minimal stimulation. The present study supports the observed immunomodulatory property of the Eastern Nigeria mistletoe and thus confirms the efficacy of this plant in mitigating against wide array of disease conditions orchestrated by immunodeficiency.

1063 Changes in Immunomodulatory Constituents of Human Milk in Response to Active Infection in the Nursing Infant

1063 Changes in Immunomodulatory Constituents of Human Milk in Response to Active Infection in the Nursing Infant

Preliminary fractionation indicates that flavonoids, steroids and terpenoids are the main immunomodulatory constituents of Loranthus micranthus (Linn)

In recent times, we have established the immunomodulatory effects of the Eastern Nigerian mistletoe, Loranthus micranthus [1, 2] as well as its antimicrobial property [3,4]. In our continued efforts to isolate the active constituents, five solvents of varying polarity namely; n-hexane, chloroform, ethyl acetate, acetone and methanol were respectively and successively employed in the complete fractionation of the crude aqueous methanol extract of Loranthus micranthus Linn., harvested from Kola acuminata. The fractions were dried in vacuo using a rotary evaporator maintained at a temperature of 40±5 oC. The different fractions were screened for immunomodulatory activity using a well established model;- the cellular- mediated delayed type hypersensivity test in experimental mice. This was performed by administering intraperitoneally, two different dose levels: 250 and 500mg/kg of each fraction against standard positive and negative controls. Results of the study established dose dependent immunostimulatory (upregulatory) effects. The five fractions of the extract exhibited different percentage stimulations compared to controls (p&lt;0.05). At the dose levels of 500 and 250mg/kg body weight, the percentage stimulation observed were as follows; chloroform fraction-311.11% and 122.22%, ethyl acetate fraction-193.38% and 95.56%, n-hexane-155.56 and 3.50%, acetone fraction-95.56% and 51.11% and methanol fraction-68.89% and 24.44% respectively. Levamisole, a known potent immunostimulant, afforded a stimulation of 68.89% at a dose of 2.5mg/kg. The phytochemical evaluation of the fractions carried out showed that the most active fractions were either chiefly steroidal, terpenoidal or flavonoidal. This work suggests that the main constituents of our local mistletoe responsible for immunostimulation are the flavonoids, steroids and terpenoids. Glycosides, carbohydrates, tannins and alkaloids appear to augment the measured activities.

Immunomodulatory constituents of human milk change in response to infant bronchiolitis

Although epidemiological evidence is generally supportive of a causal association between respiratory syncytial virus (RSV) bronchiolitis during infancy and the development of persistent wheeze/asthma, if not allergy, the mechanism by which this occurs and an explanation for why all children do not succumb remains to be elucidated. Breast feeding has been found to confer a protective effect against respiratory infections such as RSV bronchiolitis and allergy; however, again there is little direct evidence and no clear mechanism. In this study, we examined whether human milk immunomodulatory factors (cells, cytokines) change in response to clinically diagnosed, severe bronchiolitis in the recipient breast-fed infant. We examined milk from 36 breast feeding mothers of infants hospitalized with bronchiolitis and compared them with milk from 63 mothers of postpartum age-matched healthy controls. Milks from mothers of infants hospitalized with bronchiolitis had significantly greater numbers of viable cells when compared with the milks obtained from mothers of healthy infants (1.3 +/- 0.4 vs. 0.3 +/- 0.03 x 10(6) cells/ml, mean +/- s.e.m.; p < or = 0.001). Further, the cells obtained from the mothers of infants hospitalized with bronchiolitis were found to produce a skewed cytokine profile ex vivo in response to stimulation by live RSV but not when cultured with a non-specific mitogen (concanavalin A). This study provides preliminary evidence for an immunological link between mothers and their breast-fed infants during severe respiratory infections as well as a possible contributing factor to the development of persistent wheeze in these infants.

Isolation and Characterisation of Antiviral and Immunomodulatory Constituents from Nigerian mistletoe, Loranthus micranthus

Isolation and Characterisation of Antiviral and Immunomodulatory Constituents from Nigerian mistletoe, Loranthus micranthus

Nine Constituents Including Six Xanthone-Related Compounds Isolated from Two Ascomycetes, Gelasinospora santi-florii and Emericella quadrilineata, Found in a Screening Study Focused on Immunomodulatory Activity

Five metabolites tentatively called GS-1 (1)-5 (5) from Gelasinospora santi-florii, and four tentatively called EQ-4 (6), EQ-6 (7)-8 (9) together with 1-4 from Emericella quadrilineata have been isolated in a screening study on immunomodulatory fungal constituents. Among these nine metabolites, EQ-7 and 8 have been unknown. This time, the structures of GS-4 which has previously been isolated, EQ-7, and -8 have been determined to be (4R,4aS,9aR)-1,9a-dihydronidulalin A (4), (4S,4aR,9aR)-4a-carbomethoxy-1,4,4a,9a-tetrahydro-4,8-dihydroxy-6-methylxanthone (8), and 9-hydroxymicroperfuranone (9), respectively, and the six other metabolites have been identified. On bioassay, a dihydroxanthone, nidulalin A (1), a hexaketide, sordarial (5), and a xanthone, pinselin (7) have displayed significant immunosuppressive activities. The structure-activity relationships of these constituents have also been discussed.