Mori folium is also used agriculturally for feeding the silkworms, and in many countries like Turkey and Greece, Mori fructus has a role in food supply [
The current study thus aims to identify potential clinical areas of additional use of Mori folium in KM practice by reviewing ethnopharmacologic and clinical literature from other medical systems and comparing the results with a narrative review of Korean medical literatures. The specific procedures and methods are described in the following section.
Three electronic databases including PubMed (
Herbs are usually administered as a multiherbal prescription and seldom used as single herb in KM. Assessment of full texts provided only one Korean ethnopharmacologic study of Mori folium in single herb. Since this was deemed insufficient to serve as a basis for comparison, a narrative review on effect of Mori folium in KM was separately performed.
Ethnopharmacologic studies providing uses and effects attributed specifically to Mori folium alone were included, but multiherbal prescriptions were excluded. Studies providing secondhand information only were excluded to avoid duplication.
Clinical studies on isolated substances from Mori folium were excluded for this review since they cannot represent the whole range of substances present in the material as used in KM practice. Research on Mori folium products with certain fortified substances was included only when new substances were not included. Case reports were excluded since they were deemed not to represent usage. Other disputes were settled through consensus among authors.
Out of 3,421 articles identified in the search process, one KM ethnopharmacologic field study was analyzed separately in the KM narrative review, and 18 articles were included in this review.
All articles were independently reviewed by three reviewers (Jeon, Lim, and Joh) and data was extracted by predefined criteria (see Table
Predefined criteria for data extraction.
Ethnopharmacologic studies | ||||
---|---|---|---|---|
Study & text details | Uses |
Culture or nationality | ||
ID (e.g., first author) |
Disorder treatment |
Nationality of subjects | ||
|
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Clinical studies | ||||
Study details | Uses | Population | Material | Outcome measures & results |
|
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ID (e.g., first author) |
Disorder treatment |
Diagnosis |
Material used (intervention & control) |
Primary outcome measures |
There is currently no validated tool for assessing ethnopharmacologic research quality and methodological quality of clinical studies was assessed with JADAD scale [
The data analysis was conducted using the following process. Clinical uses and nationality or cultural origin of research subjects in ethnopharmacologic studies were analyzed and summarized. Clinical trials were first grouped according to ICD-10 subchapters of usage. Subsequently, exploration of the significant factors for the clinical characteristics of each group was conducted.
A literature review was separately performed as previously mentioned in Section
Clinical usage data attributed to Mori folium were extracted, but effects of multiherbal prescriptions were excluded. To preserve the cultural intonations of the data, uses were first standardized into 2nd Korean Standard Classification of Diseases-Oriental Medicine (KCD-OM2) codes which employ KM diagnostic terminology and then translated into pertaining ICD-10 category codes based on the diagnosis matching chart of KCD-OM2. Closest matches were used in both coding steps. The same ICD-10 categories appearing multiple times in a single text were counted as one use.
3421 potentially relevant articles for the global literature review were found on initial search of databases. Figure
Ethnopharmacologic studies on Mori folium.
Author (year) | Relevant ICD-10 category | Description of use in original article | Culture/nationality |
---|---|---|---|
Menale and Muoio (2014) [ |
I10 essential (primary) hypertension | High blood pressure | Italy |
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Bibi et al. (2014) [ |
R05 cough | The leaves were boiled in water (Joshanda) and given for cough due to throat pain | Pakistan |
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Ullah et al. (2013) [ |
J40 bronchitis, not specified as acute or chronic |
White mulberry leaves are expectorant, encouraging the loosing and coughing up of catarrh, and are prescribed in China as a treatment for coughs. The leaves are also taken to treat fever, sore and inflamed eyes, sore throats, headache, dizziness, and vertigo | Pakistan |
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|||
Tetik et al. (2013) [ |
n/a | Reducing |
Turkey |
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Gakuya et al. (2013) [ |
H54 visual impairment including blindness | Blindness | Kenya |
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Oliveira et al. (2012) [ |
C80 malignant neoplasm, without specification of site | Cancer | Brazil |
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Sathiyaraj et al. (2012) [ |
N46 male infertility |
Anti-infertility | India |
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Sharma et al. (2012) [ |
R17 unspecified jaundice | Leaf juice mixed with one cup of curd is given once a day till the patient is cured | India |
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Adhikari et al. (2008) [ |
L81 other disorders of pigmentation | Hyperpigmentation | Nepal |
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Au et al. (2008) [ |
M79 other soft tissue disorders | Neuritis | China |
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Arýkan et al. (2009) [ |
E10 type 1 diabetes mellitus | Type 1 diabetes in children | Turkey |
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Samy et al. (2008) [ |
T63 toxic effect of contact with venomous animals | Snakebite treatment | India |
Clinical trials using Mori folium or derived products.
Author & year | Study type | Condition & ICD-10 | Participants & sample size | Material used | Dosage & duration | JADAD score | Primary outcome measures | Main results |
---|---|---|---|---|---|---|---|---|
Banu et al. (2015) [ |
CC | Type 2 diabetes (E11) | 48 type 2 diabetics on oral medication (28 intervention + 20 black tea placebo) | Tea |
1 cup (70 mL), single dose | — | Plasma glucose change before meal with tea and 90 minutes afterwards | Plasma glucose levels in control and intervention groups before meal and 90 minutes after being changed from 178.55 ± 35.61 to 287.20 ± 56.37 (control) and 153.50 ± 48.10 to 210.21 ± 58.73 (intervention) ( |
|
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Chung et al. (2013) [ |
RCT | Glucose suppression (n/a) | 50 healthy people between ages 20 and 50 (10 + 10 + 10 + 10 + 10) |
Aqueous extract |
0 g, 1.25 g, 2.5 g, and 5 g extract, single dose | 3 (1 + 0 + 1 + 0 + 1) | Plasma glucose level at 0, 15, 30, 60, 90, and 120 minutes after maltose intake | Intake of 2.5 g or 5 g with maltose suppressed glucose elevation significantly compared to control ( |
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Asai et al. (2011) [ |
RCT + CR |
Diabetes NOS (E14) | 76 adults with 110–140 mg/dL FPG (38 intervention + 38 placebo) | Enriched extract |
6 mg DNJ equivalent extract, t.i.d., 12 weeks | 4 (1 + 0 + 1 + 1 + 1) | Fasting plasma glucose, insulin, HbA1c, glycated albumin, 1,5-anhydroglucitol at weeks 0, 4, 8, 12, and 16 | No significant difference was found between groups except for 1, 5 AG at weeks 8 & 12 ( |
|
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Srichaikul (2012) [ |
RCT | Other mental disorders (F06) | 20 women with mild cognitive impairment (5 + 5 + 5 + 5) |
Extract |
200 mg, q.d., 3 months | 2 (1 + 0 + 1 + 0 + 0) | SAGE, MMSE scale score changes at start and end of treatment period | Mean SAGE score rank changed from 14.1, 12.7, 7.3, and 7.9 to 17.70, 8.7, 11.0, and 4.6. Mean MMSE score rank changed from 17.4, 10.5, 6.7, and 7.4 to 17.6, 10.1, 8.5, and 5.8. |
|
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Nakamura et al. (2009) [ |
CR | Glucose suppression (n/a) | 10 healthy volunteers | Ethanol extract |
1.2 or 3 g, single dose | — | Plasma glucose (Glu.) & insulin (Ins.) (every 30 minutes for 3 hours) | Glucose and insulin elevation was suppressed in 1.2 and 3 g group compared to control at different time points (1.2 g Glu.: 30, 120 min/Ins.: 30 min/3 g Glu.: 30.90, 120 min/Ins.: 30 min/all |
|
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Yang and Han (2006) [ |
RCT | Type 2 diabetes (E11) | 25 type 2 diabetics on oral medication (14 intervention + 9 control) | Aqueous extract |
500 mg b.i.d., 12 weeks | 4 (1 + 0 + 1 + 1 + 1) | Fasting plasma glucose, HbA1c, serum lipids at start and end of treatment period | HbA1c, LDL-C, and TG decreased in intervention compared to control ( |
RCT, randomized controlled trial; CR, crossover; CC, case-controlled. All medications were taken orally.
Data extraction process of the current review.
17 records of clinical uses in 13 categories were found from 12 non-Korean ethnopharmacologic studies with 8 cultural origins. Table
Mori folium was used in multiple studies for respiratory tract disorders at Pakistan. It was used in 3 instances such as an expectorant and sore throat treatment [
Other uses include dizziness and vertigo treatment, antipyretic, analgesic [
Six clinical trials within predetermined criteria were found and had small or moderate sample size. Five studies were on diabetes or postprandial glucose suppression, and one study was on cognitive function. Table
The single study on cognitive function was a randomized clinical trial with poor methodological quality. It suggested a possible improvement of cognition in mild cognitive impairment patients [
One ethnopharmacologic study provided a record of treatment of sore throat [
Korean medical literature on Mori folium.
Author | Published | Name of the book | Relevant ICD-10 category |
---|---|---|---|
Unknown | 0th–2nd |
|
R50 fever of other and unknown origin |
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Ge Hong | 3rd |
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A09 other gastroenteritis and colitis of infectious and unspecified origin |
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Tao Hongjing | 2nd-3rd |
|
T63 toxic effect of contact with venomous animals |
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Su Jing | 7th |
|
R52 pain, not elsewhere classified |
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Meng Shen | 7-8th |
|
R63 symptoms and signs concerning food and fluid intake |
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Chen Zangqi | 8th |
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K52 other noninfective gastroenteritis and colitis |
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Cao Beng | 8th |
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K52 other noninfective gastroenteritis and colitis |
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Rihuazi | 10th |
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M25 other joint disorders, not elsewhere classified |
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Unknown | 10–13th |
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M06 other rheumatoid arthritis |
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Unknown | 14th |
|
R61 hyperhidrosis |
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Yu Hyo-Tong | 15th |
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N61 inflammatory disorders of breast |
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Liu Wentai | 16th |
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A09 other gastroenteritis and colitis of infectious and unspecified origin |
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Chén Jiä-Mó | 16th |
|
H04 disorders of lacrimal system |
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Li Chan | 16th |
|
H04 disorders of lacrimal system |
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Li Shizhen | 16th |
|
R05 cough |
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Miu Xi-Yong | 17th |
|
R61 hyperhidrosis |
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Miu Xi-Yong | 17th |
|
H11 other disorders of conjunctiva |
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Wu, Youxing | 17th |
|
R50 fever of other and unknown origin |
|
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Heo Jun | 17th |
|
K52 other noninfective gastroenteritis and colitis |
|
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Lun Zhu | 18th |
|
H04 disorders of lacrimal system |
|
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Wú Yíluò | 18th |
|
T14 injury of unspecified body region |
|
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Huang Gongxiu | 18th |
|
H54 visual impairment including blindness (binocular or monocular) |
|
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Guö Rû-Cóng | 19th |
|
R61 hyperhidrosis |
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Unknown | 19th |
|
R50 fever of other and unknown origin |
|
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Yang Shitai | 19th |
|
H11 other disorders of conjunctiva |
|
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Chen Qirui | 19th |
|
H54 visual impairment including blindness (binocular or monocular) |
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Beijing Institute of Chinese Medicine | 20th |
|
H54 visual impairment including blindness (binocular or monocular) |
|
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Szechuan Chinese Materia Medica Editing Committee | 20th |
|
H54 visual impairment including blindness (binocular or monocular) |
|
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Shin Gil-Gu | 20th |
|
R50 fever of other and unknown origin |
|
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Lee Sang-In | 20th |
|
H54 visual impairment including blindness (binocular or monocular) |
|
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Nan Jing Traditional Chinese Medical School | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Lee Sang-In | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Zhen Xunying | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Nationwide Chinese Medical Herb Compilation Committee | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Jiangxi Health and Welfare Ministry | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Zhou jinzhong | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Lin Tongguo | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Color Illustrated Chinese Medicine Pharmacopoeia Editing Committee | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Editing Committee | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Great Collection of Chinese Medicine Editing Committee | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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National Korean Medical College Textbook Editing Committee | 20th |
|
J00 acute nasopharyngitis [common cold] |
|
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Kim Ho-Chul | 21th |
|
R50 fever of other and unknown origin |
|
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Song and Kim | 21th |
|
J02 acute pharyngitis |
English translations of author and text names were used whenever available.
The current study examined global and Korean literature on medical use of Mori folium to discover additional clinical applications in traditional Korean medicine. In traditional Korean medicine (Table
However there are some other clinical uses uniquely for traditional Korean medicine including treatment of hyperhidrosis, gastrointestinal tract, and joint disorders and use as hair tonic that can be adopted in other medical systems. Along with these, treatments of infertility [
There have been many clinical reports of Mori folium on blood glucose and diabetes (Tables
As for the summary and analysis in this study, the authors coded reported clinical uses into ICD-10 categories to compare their clinical effects. Though ethnopharmacologic studies sometimes have used ICD-10 chapters to categorize medicinal effects [
Although the ICD-10 coding system has universal use and usefulness for comparing studies from the world in scientific ways, there might be inevitable losses during the translation due to the nature of Western medicine underneath the coding system. For example, ICD-10 does not differentiate fever caused by liver heat and kidney deficiency, which has different accompanying signs and symptoms, and warrants completely different ways of treatment. Therefore, it should be noted that the findings in this study should be thoroughly explored with respect to their originating culture or nationality before the clinical application. And, the indicators of clinical importance and reliability were also not provided for the majority of studies. Therefore, all the potential clinical uses found in this review should be reexamined with further studies regardless of citation frequencies in here.
In this study, we excluded the clinical reports with multiherbal decoction including Mori folium as one of the ingredients and rather included description from medical textbooks, classics, and pharmacopoeia, since clinical action and effectiveness of a given herb may vary according to its role in the prescription and so it is hard to analyze its clinical usefulness. As the medical herbs are usually used as a multiherbal decoction in traditional Korean and Chinese medicine, there would be a possibility that Korean ethnopharmacologic usage and Chinese clinical studies might be unsatisfactory in this review [
In conclusion, we performed a review on clinical use of Mori folium with three database and traditional Korean medical textbooks and pharmacopoeia and analyzed its clinical use with ICD-10 code. From 159 relevant studies and 17 clinical usages, infertility, jaundice, cognitive disorder, and hyperpigmentation were identified as potential clinical uses, and diabetes was the one deserving more emphasis. This study would contribute to the thorough understanding on the clinical usefulness of
The authors declare that there is no conflict of interests regarding the publication of this paper.