Lignosus Rhinoceros TM02® as a Complementary Therapy for Uncontrolled Asthma: A Prospective, Open-label, Single-arm, Phase II Study
Phase: PHASE2
Conditions: Asthma
Sponsor: University of Malaya

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Lignosus rhinocerus TM02® as an immunomodulatory agent for the 
treatment of uncontrolled asthma: A prospective, open-label, single-arm, 
Phase II study.  
 
Principal Investigator:  
 
Assoc. Professor Dr. Poh Mau Ern,  
Consultant Respiratory Physician,  
Department of Medicine, Faculty of Medicine,  
University of Malaya, Kuala Lumpur.  
 
Sub-Investigators:  
 
Department of Medicine, University of Malaya 
Assoc. Professor Dr Pang Yong Kek 
Dr Wong Chee Kuan 
Dr Tan Jiunn Liang 
Dr Loh Thian Chee 
Dr Vijayan Munusamy 
Dr Chin Ka Kiat 
Dr Nur Husna binti Ibrahim  
 
Kulliyyah of Medicine, International Islamic University Malaysia  
Dr Muhammad Adil Zainal Abidin  
 
Department of Molecular Medicine, University of Malaya  
Assoc. Professor Dr Fung Shin Yee 
 
Clinical Investigation Center, UMMC (Research Assistants) 
Kokila Vani Perumal 
Dr Dian Syuhada 
 
Time Frame of study: 
Expected start date : 01/07/2022 
Expected end date : 31/05/2023 
 
Research Background 
 
Introduction  
Lignosus rhinocerus, the Tiger Milk Mushroom, belongs to the Polyporaceae family 
and is one of the most important medicinal mushrooms used by natives in Southeast 
Asia and one of the most popular medicinal mushrooms used by indigenous 
communities of Peninsular Malaysia. It is known locally as “cendawan susu rimau” - 
literally “mushroom of tiger’s milk.” It has traditionally been used by the Malays, 
Chinese and indigenous communities in Malaysia to treat a variety of diseases, 
including cough, asthma, fever, chronic hepatitis, gastric ulcer, liver and breast cancer 
and as a general tonic.  In 2002, our former prime minister, Tun Dr. Mahathir 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Mohamad, mentioned that his chronic cough had been cured by this medicinal 
mushroom during his opening speech at BioMalaysia.   
Since the inception of scientific research in 2002 into Lignosus rhinocerus TM02® 
(Tiger Milk mushroom) and its associated bioactivities by the Medicinal Mushroom 
Research Group (MMRG), [Faculty of Medicine, University of Malaya], they have 
revealed various relevant, solid scientific data that supports the translation of L. 
rhinocerus research into practical use. They have proven it to be safe for consumption 
(Lee et al, 2011, 2013). They have also identified the extract and fraction from Lignosus 
rhinocerus TM02® that play numerous roles in immunomodulation (Yap et al , 2020) , 
anti-inflammatory (Lee et al, 2014), bronchodilating (Lee et al, 2018), anti-proliferative 
(Yap et al, 2013, 2017), antioxidative (Yap et al, 2013) and antiglycation (Yap et al , 
2018).  
MMRG has also subjected Lignosus rhinocerus TM02® to corticosteroid screening by 
Toxicology Laboratory, National Poison Centre. The results confirmed the absence of 
corticosteroid 
(Dexamethasone, 
Betamethasone, 
Costisone, 
Hydrocortisone, 
Prednisone, Prednisolone, Methyl prednisolone, Triamcinolone) as part of its 
ingredient.   
Lignosus rhinocerus TM02® is marketed as “Tigerus Tiger Milk Mushroom Sclerotia” 
with a registration number of MAL 13025025TC. (Please see supporting documents 
for NPRA documents).  
 
Rationale of Study  
Asthma and FeNO  
Asthma is a disease with marked heterogeneity in its clinical course and in its response 
to treatment. Variability in the type of airway inflammation may underlie this 
heterogeneity.  Despite treatment with inhaled glucocorticoids, many patients 
continue to have uncontrolled asthma that requires more intensive therapy.  Based 
on the ethnobotanical uses of Tiger Milk mushroom in treating asthma, its significant 
anti-inflammatory activity and also the positive feedbacks received from asthmatic 
volunteers using LiGNO™ Tiger Milk Mushroom, it is worthwhile to explore the 
potential of Tiger Milk Mushroom to be used as an immunomodulatory treatment to 
support conventional therapy through a proper designed clinical study.  This will allow 
patients with uncontrolled asthma to obtain access to a new complementary therapy 
which they may benefit from.  The objective of the study is to investigate the efficacy 
of L. rhinocerus to be used as a complementary therapy in improving symptoms, 
preventing exacerbations and reducing underlying airway inflammation in asthma 
patients. 
FENO (fractional exhaled nitric oxide) is the only available point of care test to assess 
type-2 inflammation in asthma. Raised FENO with blood eosinophilia should be 
regarded as treatable traits of type 2 inflammation. FENO maybe useful for providing 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
feedback to both physicians and patients taking asthma therapy (in particular inhaled 
corticosteroids, ICS) particularly when the spirometry is normal.  
FENO values can be influenced by several non-disease-related factors, thus filling in a 
questionnaire for NO measurement is recommended. Confounding factors could be 
related to the patient, like genetics, sex, weight and height, diet (i.e., coffee) or taking 
drugs such as anti-inflammatory medications; also current smoking and atopy seem 
to influence FENO levels. Allergen exposure is associated with higher levels of FENO but 
they could decrease during the early phase of allergic response. Smoking is an 
important determinant of FENO levels and current smokers exhibit lower levels of 
FENO in comparison to ex-smokers and never smokers. Both active and passive 
smoking have effects on lowering FENO as demonstrated in healthy adults and in both 
adults and children suffering from asthma, regardless their allergy status.  
FENO could be influenced also by viral respiratory infections. Age seems to be 
important too, especially in children, but correlation between age and sex has still to 
be defined. Recently, also ethnicity seems to have a role in FENO results, impacting 
clinical management. 
Moreover, there are also technical confounding factors in FENO measurement, like the 
NO analyzer used, measurement technique, exhalation flow rate or nasal NO 
contamination. Spirometry could also influence FENO results, thus it should not be 
performed first. FENO could increase due to bronchodilation and it could decrease due 
to bronchoconstriction.  
Reference values have been described for FENO. In clinical practice, FENO <25 ppb in 
adults is considered the normal value. FENO levels between 25-50 ppb in adults (20-35 
ppb in children) should be contextualized within the clinical context. 
The eosinophilic asthma phenotype is characterized by sputum eosinophils ≥3% and 
identifies 
patients 
with 
a 
good 
response 
to 
corticosteroids 
and 
T2 
immunomodulators. FENO values >50 ppb are likely connected with airway 
eosinophilic inflammation and this data may be used to predict a response to anti-
inflammatory therapy, while low FENO <25 ppb correlates with less eosinophilic 
inflammation and responsiveness to corticosteroids. Diagnostic FENO cut point in well 
controlled asthma is usually indicated by normal values. FENO >30 ppb is usually 
associated with uncontrolled asthma. 
According to GINA guidelines, following the diagnosis of severe asthma, FENO≥20 ppb 
is considered the cut-off characterizing Type 2 inflammation severe asthma and it is 
used to assess this asthma phenotype, together with other markers like blood and 
sputum eosinophils. It has been suggested a FENO cut point of 21 ppb best fits ≥3% 
sputum eosinophils in corticosteroid-naive patients.  
Very few data from studies analyzing clinically important change of FENO in individual 
patients is available and different are the results depending on the considered 
outcome. Considering simply the within-subject coefficient of variation, in healthy 
subject is approximately 10% (corresponding to a raw change up to 4 ppb) while it 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
increases to about 20% in patients with asthma, therefore leading the ATS experts to 
recommend a change of at least 20% to indicate a significant rise or fall in FENO over 
time or following an intervention.  
The ATS makes the following recommendation:  
• 
We recommend that low FENO less than 25 ppb be used to indicate that 
eosinophilic inflammation and responsiveness to corticosteroids are less 
likely.  
• 
We recommend that FENO greater than 50 ppb be used to indicate that 
eosinophilic inflammation and, in symptomatic patients, responsiveness to 
corticosteroids are likely.  
• 
We recommend that FENO values between 25 ppb and 50 ppb  should be 
interpreted cautiously and with reference to the clinical context.  
• 
We suggest using a reduction of at least 20% in FENO for values over 50 
ppb or a reduction of more than 10 ppb for values lower than 50 ppb as 
the cut point to indicate a significant response to anti-inflammatory 
therapy.   
We hypothesize that  Lignosus rhinocerus TM02® can be used as a complementary 
supplement to support conventional therapy in asthmatic patients through a properly 
designed clinical study. 
Research Questions  
1. Can  Lignosus rhinocerus TM02® reduce airway inflammation, improve symptoms 
and prevent exacerbations in asthma patients. 
2. Can  Lignosus rhinocerus TM02® be used alongside conventional Western 
medications as per global guidelines to reduce airway inflammation, improve 
symptoms and prevent exacerbations in asthma patients. 
Problem Statement  
To date, there have not been any safe treatments that are void of side effects for the 
current respiratory related illnesses and/or pandemics. Based on the current handling 
procedures in health care centers, and as recently discussed in the Chinese Medicine 
Task Force Malaysia COVID19, it was revealed that natural products play an important 
role in alleviating and as adjunct therapy to present day Western medications. It is 
imperative that we thoroughly investigate the potential mode of action of these 
natural compounds, especially ones that has been proven safe for human 
consumption and with other known health benefits. In light of the current pandemic, 
Lignosus rhinocerus TM02®, which has been proven safe for consumption, contains 
synergictically acting biomolecules that will improve the quality of life of respiratory-
related illnesses. This area of research is new, novel and has the potential to reveal 
valuable data for further pharmaceutical intervention studies. 
 
 
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Objectives  
 
The primary objective is to assess the effect of Lignosus rhinocerus TM02® in reducing 
airway inflammation by measurement of exhaled nitric oxide (FENO) and to assess the 
effect of Lignosus rhinocerus TM02® in bronchodilation by measurement of trough 
forced exhaled volume in 1 second (FEV1). 
The secondary objective is to assess the effect of Lignosus rhinocerus TM02® to be 
used as complementary therapy to improve symptoms and prevent exacerbations in 
asthma patients as assessed by the asthma control questionnaire (ACQ-7). 
The tertiary objective is to assess the safety profile of Lignosus rhinocerus TM02® as 
complementary therapy in asthma patients.  
 
STUDY DESIGN AND SAMPLE SIZE 
 
This is a prospective, open-label, Phase II study. 
The study will consist of a single treatment phase including: 
• 
Screening period  
• 
12 weeks (90 days) of treatment period.   
 
The planned sample size for this study is 17 subjects.  In order to evaluate primary 
and secondary outcomes, study assessments will be conducted at Day 0, 30, 60 and 
90 of treatment. 
 
The MCID for FEV1 is 12% and 200 ml measured by spirometry obtained at baseline 
(immediately prior to the start of the treatment) with the results obtained 2 hour 
after administration of study medication (2-hour postdose FEV1) after 12 weeks of 
treatment. 
 
The MCID for FENO is a reduction of at least 20% in FENO for values over 50 ppb or more 
than 10 ppb for values lower than 50 ppb will be used as the cut point to indicate a 
significant response to treatment.   
 
 
Endpoints 
Primary Endpoints 
 
• 
Change in mean trough FEV1 expressed as mililitres after 90 days of 
treatment 
• 
Change in mean ACQ-7 scores after 90 days of treatment   
 
• 
The threshold for change in ACQ-7 scores that is considered clinically 
important (MCID) is 0.5.  
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
 
 
 
Secondary Endpoints 
   
• 
Changes in mean FeNO (ppb) after 90 days of treatment  
• 
Change in mean eosinophil count (cells/dL) after 90 days of treatment   
• 
Changes in mean serum immunoglobulin E level (IU/ml) after 90 days of 
treatment 
 
 
Study Population 
The target population for this study consists of 10 Patients with uncontrolled asthma 
aged 18 and above.  Each subject will have to fulfil the inclusion criteria listed below.  
Subjects will not be included in the study if they meet any of the exclusion criteria 
listed below.   
Inclusion Criteria 
All adults aged 18 years and above with a prior documented diagnosis of atopic (Th2-
driven) asthma by a physician based on Global initiative for Asthma (GINA) 2020 
Guidelines whose asthma is uncontrolled on ICS/LABA combination therapy based on 
the following criteria:  
a)  
A well documented requirement for regular treatment with a minimum dose 
of 
either 
fluticasone 
/salmeterol 
combination 
therapy 
or 
budeosnide/formoterol combination therapy in the 12 months prior to 
screening with or without maintenance of oral corticosteroids (OCS).  
b) 
 Forced expiratory volume (FEV1) > 50% to <80% predicted normal during the 
screening phase (3 attempts maximum) and on the randomization day prior to 
the first dose of IMP.  
c) 
Reversibility of at least 12% and 200 ml in FEV1 after 200 ug to 400 ug (2 to 4 
inhalations) of salbutamol during the screening phase (3 attempts maximum), 
or documented history of reversibility test that met these criteria within 12 
months prior to screening. 
d)  
FENO of > 25 ppb measured at baseline screening.  
 
• 
Absence of a recent exacerbation 6 weeks prior to enrolment 
• 
Non-smoker patient for at least six months and with a prior tobacco 
consumption < 10 packs/ year 
• 
Patient with normal organ function  
• 
Patient weight > 41 kg and body mass index (BMI) between 18 and 35 kg/m2 
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
 
Exclusion Criteria 
• 
Asthmatic patient still exposed to allergens or to triggering factors 
influencing asthma control 
• 
Female subjects who are pregnant or lactating 
• 
Chronic obstructive pulmonary disease (COPD) and/or other lung 
diseases imparing pulmonary function test  
• 
Within 6 weeks prior to screening, patient who received oral 
corticosteroids for any other reason than to treat asthma (patients 
needing long term OCS to control asthma)  
• 
 Patient with history of acute infectious sinusitis or respiratory tract 
infection within 4 weeks prior to screening visit  
 
• 
 Patient presenting with cardiac disorders defined by at least one of the 
following conditions:  
 
a) Patient with recent cardiac history (within 6 months) of : 
• acute coronary syndrome 
• acute heart failure (Class III or IV of the NYHA classification) 
• significant 
ventricular 
arrhythmia 
(persistent 
ventricular 
tachycardia, ventricular fibrillation, resuscitated sudden death)  
b) Patient with cardiac failure class III or IV of the NYHA classification  
c) Patient with sever conduction disorders which are not prevented by 
permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block) 
d) Syncope without known aetiology within 3 months 
e) Uncontrolled severe hypertension, or symptomatic hypertension  
 
• 
Patient with active lung disease other than asthma (eg. Chronic 
bronchitis)  
• 
Patient who had a major surgery within 4 weeks prior to screening visit 
• 
Patient with a life expectancy of less than 6 months 
• 
Patient with history of primary malignancy < 5 years, except treated 
basal cell skin cancer or cervical carcinoma in situ.  
• 
Patient with any severe and/or uncontrolled medical condition aside 
from asthma 
• 
Patient with a known diagnosis of human immunodeficiency virus (HIV) 
infection  
• 
Patient with history of poor compliance or history of drug/alcohol 
abuse.  
• 
Participation in a clinical study with exposure to any non-registered 
drug or botanical product within 30 days prior. 
• 
Individual has a condition the investigator believes would interfere 
with his or her ability to provide informed consent, comply with the 
study protocol, which might confound the interpretation of the study 
results or put the person at undue risk 
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Early Withdrawal 
 
Subject discontinuation should be considered at the discretion of the principal 
investigator.  The circumstances of any discontinuation have to be documented in 
detail.  If possible, the evaluations planned for the end of study will be carried out at 
the time when the subject is withdrawn from the study.   
 
 Criteria for removal of subjects from the study will include: 
 
Personal reasons 
As stated in the Informed Consent Form, a subject may withdraw from the study for 
any reason at any time. 
 
Clinical judgment of physician 
A subject may be withdrawn from the study if, in the opinion of the principal 
investigator, it is not in the subject's best interest to continue.  This includes but is not 
limited to adverse events or serious adverse events related to the investigational 
product causing clinically significant illness; the need for prohibited concomitant 
medication; female subject who becomes pregnant during the course of the trial. 
 
Protocol violation 
Any subject found to have entered this study in violation of the protocol will be 
discontinued from the study at the discretion of the principal investigator.  This will 
include any subject found to have been inappropriately enrolled (did not meet 
eligibility criteria).  Subject non-compliance includes either not showing up for study 
visits, not taking investigational product as directed, or refusing to undergo study visit 
procedures.  Subjects who are found to be less than 75% compliant with test article 
usage at any study visit will be withdrawn.  Subjects who are found to be taking 
prohibited medications or supplements without the knowledge of the principal 
investigator will also be withdrawn.  Any major protocol deviations (i.e., those that 
increase the risk to subjects and/or compromise the integrity of the study or its 
results) will result in subject discontinuation. 
Study Procedures 
Pre-study Visit (Screening)  
At screening, a Subject Information and Consent Form will be given to the potential 
subject.  The subject will read the information carefully and will be given the 
opportunity to seek more information if needed.  The subject will also be provided 
with the option of taking the consent form home to review prior to making his or her 
decision.  If agreeable, the subject will sign the consent form and receive a duplicate.  
After the subject has signed the informed consent, the screening number will be 
assigned sequentially and entered in the Screening and Enrolment Log.  Screening 
numbers will be allocated in the chronological order of the subject’s signing the 
informed consent. 
Screening includes: 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
• 
Review of medical history and concomitant therapies. 
• 
Symptoms examination  
• 
Phyiscial examination 
• 
Review of inclusion/exclusion criteria 
• 
Exhaled nitric oxide (FENO) measurements  
 
If FENO is > 25 ppb,  
 
• 
Spirometry measurement (FEV1 and FVC) 
• 
Laboratory tests (basic hematology and chemistry) 
• 
Urine pregnancy test for women of childbearing potential 
• 
ECG 
 
Baseline - (Visit 1 / Week 0/ Day 0)  
Subjects will receive the treatment regimen of LiGNO™ TMM. 
Eligible subjects will return to the clinic in a fasted condition (last food intake at least 
12 hours before the visit; subjects will be allowed to drink water) for baseline 
assessments: 
• 
vitals signs, weight and height measurement 
• 
Asthma Control Questionnaire 
• 
review of concomitant therapies  
• 
physical examination 
• 
Review of spirometry measurements (FEV1 and FVC)  
• 
Review of laboratory tests (basic hematology and chemistry) 
• 
Review of urine pregnancy test for women of childbearing potential 
• 
Review of baseline ECG 
 
 After all baseline assessments are reviewed, subjects will be dispensed the 
investigational product. 
 
Subjects will receive LiGNO™ TMM.  Subjects will be instructed in detail by site 
personnel about the dosing regimen.  The first dose of study product is to be taken 
the day after the Baseline visit, treatment Day 1, consisting of :  
• 
2 capsules of 250 mg L. rhinocerus, once a day after breakfast and dinner 
daily for 4 weeks 
Subjects will be given a diary card to record their symptoms every day.  Subjects will 
be reminded to fast (12 hours) prior to their study visits.  The next visit will be 
scheduled for Week 4/Day 30 . 
Investigational Study Visit (Visit 2 / Week 4 / Day 30)  

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Subjects will return the clinic on Week 4 (Day 30).  Any remaining investigational 
product or empty packaging will be returned and a new supply dispensed.   
Study visit assessments will include: 
• 
vitals signs, weight measurement 
• 
review of concomitant therapies 
• 
review of adverse events  
• 
review of the diary card record 
• 
symptoms examination  
• 
compliance calculation 
• 
Asthma Control Questionnaire  
• 
Laboratory tests (basic hematology and chemistry) 
• 
Exhaled nitric oxide (FENO) measurements 
• 
ECG 
 
Subjects will receive LiGNO™ TMM.  Subjects will be instructed in detail by site 
personnel about the dosing regimen.  Dosing will be escalated to   
• 
2 capsules of 250 mg L. rhinocerus, twice a day after breakfast and dinner 
daily for 8 weeks 
Subjects will be reminded to fast (12 hours) prior to their study visits.  The next visit 
will be scheduled for Day 60. 
Investigational Study Visit (Visit 3 / Week 8 / Day 60)  
Subjects will return the clinic on Week 8 (Day 60).  Any remaining investigational 
product or empty packaging will be returned and a new supply dispensed.   
Study visit assessments will include: 
• 
vitals signs, weight measurement 
• 
review of concomitant therapies 
• 
review of adverse events  
• 
review of the diary card record 
• 
symptoms examination  
• 
compliance calculation 
• 
Asthma Control Questionnaire  
• 
Laboratory tests (basic hematology and chemistry) 
• 
Exhaled nitric oxide (FENO) measurements  
• 
ECG 
 
Subjects will be reminded to fast (12 hours) prior to their study visits.  The next visit 
will be scheduled for Week 12/Day 90. 
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
End of Treatment  Visit (Visit 4 / Week 12/ Day 90) - CIC 
Subjects will return the clinic on Day 90.  Any remaining investigational product or 
empty packaging will be returned.   
Study visit assessments will include: 
• 
vitals signs, weight measurement 
• 
review of concomitant therapies 
• 
review of adverse events  
• 
review of the diary card record 
• 
symptoms examination  
• 
compliance calculation 
• 
Asthma Control Questionnaire  
• 
Laboratory tests (basic hematology and chemistry) 
• 
Exhaled nitric oxide (FENO) measurements, followed by  
• 
Spirometry measurement (FEV1 and FVC) 
• 
ECG 
 
This visit will conclude the study.  
 
Grant and Funding 
 
This research is supported by the University Malaya Faculty Research Grant (UMFRG) 
2020.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
References 
 
Preclinical toxicology and safety studies 
1.  
S.S. Lee, N.H. Tan, S.Y. Fung, J. Pailoor, S.M. Sim (2011) Evaluation of the sub-
acute toxicity of the sclerotium of Lignosus rhinocerus (Cooke), the Tiger Milk 
mushroom, Journal of Ethnopharmacology , 138:192-200 
2.  
Sook Shien Lee, Francis Kanyan Enchang, Nget Hong Tan, Shin Yee Fung, 
Jayalakshmi Pailoor (2013) Preclinical toxicological evaluations of the sclerotium of 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Lignosus rhinocerus (Cooke), the Tiger Milk mushroom, Journal of 
Ethnopharmacology,147 (157-163) 
 
Therapeutic effects: 
• 
anti-acute inflammatory (Lee et al.2014) - inhibition of TNF-alpha 
production 
Sook Shien Lee, Nget Hong Tan, Shin Yee Fung, Si Mui Sim, Chon Seng Tan, Szu Ting 
Ng (2014) Anti- inflammatory effect of the sclerotium of Lignosus rhinocerotis 
(Cooke) Ryvarden, the Tiger Milk mushroom, BMC Complementary and Alternative 
Medicine 14:359 (8 pages) 
• 
strong antioxidant, free radical scavenging (Yap et al, 2013) 
Yeannie HY Yap, Nget Hong Tan,Shin Yee Fung, Azlina A Aziz, Chon Seng Tan and Szu 
Ting Ng (2013) Nutrient composition, antioxidant properties, and anti- proliferative 
activity of wild type and cultivated strain of Lignosus rhinocerus Cooke (Tiger milk 
mushroom) sclerotium, Journal of the Science of Food and Agriculture 93(12):2945-
2952 
• 
modulates cytokines (Yap et al, 2020) 
Alvin Yap Chee Sum, Xiaojie Li, Yeannie Yap Hui Yeng, Muhammad Fazril Mohamad 
Razif, Amira Hajirah Abd Jamil, Ng Szu Ting, Tan Chon Seng, Peter Chi Keung Cheung, 
Shin-Yee Fung (2020) The Immunomodulating Properties of Lignosus rhinocerus 
TM02® Cultivar and Its Associated Carbohydrate Composition, International Journal 
of Medicinal Mushroom 10.1615/IntJMedMushrooms.2020035658 
 
Supported by  
• 
Nutritional studies  and amino acid compositions 
Yeannie HY Yap,Nget Hong Tan,Shin Yee Fung,Azlina A Aziz,Chon Seng Tan and Szu 
Ting Ng (2013) Nutrient composition, antioxidant properties, and anti- proliferative 
activity of wild type and cultivated strain of Lignosus rhinocerus Cooke (Tiger milk 
mushroom) sclerotium, Journal of the Science of Food and Agriculture 93(12):2945-
2952 
 
• 
Genome, Transcriptome and Proteome Studies 
Hui-Yeng Y Yap, Yit-Heng Chooi, Mohd Firdaus-Raih, Shin- Yee Fung, Szu-Ting Ng, 
Chon-Seng Tan, Nget- Hong Tan (2014) The genome of the Tiger Milk mushroom, 
Lignosus rhinocerotis, provides insights into the genetic basis of its medicinal 
properties, BMC Genomics 15:635 
 
Hui-Yeng Yeannie Yap, Shin-Yee Fung, Szu-Ting Ng, Chon-Seng Tan, Nget-Hong Tan 
(2015) Genome-based Proteomic Analysis of Lignosus rhinocerotis (Cooke) Ryvarden 
Sclerotium, International Journal of Medical Sciences 12(1):23-31 
 
Hui-Yeng Y Yap, Yit-Heng Chooi, Shin-Yee Fung, Szu- Ting Ng, Chon-Seng Tan, Nget-
Hong Tan (2015)Transcriptome Analysis Revealed Highly Expressed Genes Encoding 
Secondary Metabolite Pathways and Small Cysteine-Rich Proteins in the Sclerotium 
of Lignosus rhinocerotis, PLoS One http://dx.doi.org/10.1371/journal.pone.0143549 
 

Tiger Milk Mushroom Asthma Research Protocol Version 3.0 dated 14th February 2021 
Hui-Yeng Y. Yap, Shin-Yee Fung, Szu-Ting Ng, Chon-Seng Tan, Nget-Hong Tan (2015) 
Shotgun proteomic analysis of tiger milk mushroom (Lignosus rhinocerotis) and the 
isolation of a cytotoxic fungal serine protease from its sclerotium, Journal of 
Ethnopharmacology 174(2015)437 -451 
 
Other publication on human use using TM02® :  
Chen CK, Hamdan NF, Ooi FK, Wan Abd Hamid WZ. Combined effects of lignosus 
rhinocerotis supplementation and resistance training on isokinetic muscular strength 
and power, anaerobic and aerobic fitness level, and immune parameters in young 
males. Int J Prev Med 2016;7:107. 
 
FENO:  
Dweik RA, Boggs PB, Erzurum SC, e tal. An official ATS clinical practice guidelineL: 
Interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J 
Respir Crit Care Med 2011, 184 (5).  
Heffler E, Carpagnano GE, Favero E, et al. Fractional Exhaled Nitric Oxide (FENO) in the 
management of asthma: a position paper of the Italian Respiratory Society (SIP/IRS) 
and Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC). Multidiscip 
Respir Med. 2020;15(1):36.