Alpinia officinarum Hance: a comprehensive review of traditional uses, phytochemistry, pharmacokinetic and pharmacology

The dried root and rhizome of Alpinia officinarum Hance (A. officinarum) have been widely used in traditional Chinese medicine for thousands of years to alleviate pain, promote digestion, warm the stomach, and disperse cold. This review aims to comprehensively and in-depth summarize the most recent research on the traditional uses, phytochemistry, pharmacokinetics, and pharmacology of A. officinarum. By searching various databases including Web of Science, PubMed, Google Scholar, Elsevier, Springer, ScienceDirect, and China National Knowledge Infrastructure (CNKI) for literature on “A. officinarum Hance,” as well as relevant textbooks and digital documents, an overall and critical review of the subject was conducted. The traditional uses of A. officinarum were summarized, and 337 compounds from A. officinarum were summarized, including flavonoids, diarylheptanoids, volatile oils, and other compounds. Studies have found that the crude extract of A. officinarum and its compounds has a wide range of biological activities, such as improving gastrointestinal function, anti-inflammatory properties, anti-tumor activity, antibacterial properties, memory enhancement, and analgesic effects. Modern pharmacological studies have provided strong evidence and explanations for the traditional medicinal uses of A. officinarum, which brings a broad prospect for its medicinal use. However, more research is needed to explore the structure-activity relationship and potential mechanisms of action of its bioactive chemicals. Furthermore, it is essential to conduct more clinical trials in order to accelerate research and development of the drug.


Introduction
With the development of the times, people are increasingly focusing on their wellbeing.The advancement of medical technology has also begun to attract attention.While new drugs for various diseases are constantly being developed, people are actively exploring alternative therapies and natural products due to the toxic side effects of chemical drugs and the uncontrollable risks of biological agents.Alpinia officinarum Hance (A. officinarum), native to China, is one of the most important species of the Zingiberaceae family, which is widely distributed in Fujian, Taiwan, Guangdong, Guangxi, Hainan, and other provinces in China (Sun et al., 2023;Zheng et al., 2024).The detailed description of the medical applications of A. officinarum can be traced back to the book "Ming Yi Bie Lu," which was written during the Han Dynasty (Tao, 1986).As a medicinal part, the aromatic rhizome of A. officinarum mainly belongs to the spleen and stomach meridians and was widely used in the treatment of gastrointestinal diseases in ancient China (Tushar et al., 2010;Al Garni et al., 2024).
Botanical drugs have been widely used to treat many diseases for centuries due to their obvious effectiveness, fewer side effects, and relatively low cost.A. officinarum is known for its extensive clinical applications because it contains a variety of bioactive substances, including flavonoids, diarylheptanoids, volatile oils, phenylpropanoids, and glycosides (Pillai et al., 2018;Wen et al., 2024).Flavonoids and diarylheptanoids are its main components and have been proven to have a variety of pharmacological effects (Abubakar et al., 2018).In this paper, the traditional uses, chemical components, and biological activities of A. officinarum were reviewed comprehensively, which provide better guidance for the rational utilization of it.
2 Traditional efficacy and application of A. officinarum A. officinarum, which is also known as "Liangjiang" and "Xiaoliangjiang," was first recorded in the "Ming Yi Bie Lu" during the Han Dynasty (Tao, 1986).As shown in Table 1, the properties of A. officinarum have mainly been described as pungent and warm, while in some ancient books, there have been occasional records of "bitter".It has been recorded in ancient books that A. officinarum mainly enters the two meridians of the spleen and stomach, but rarely enters the heart, liver and Danzhong meridians.The records of A. officinarum in modern works on herbal all belong to the spleen and stomach meridians.Through the analysis of the records of the efficacy of A. officinarum in ancient and modern Chinese botanical drug, it was found that its common features in terms of efficacy are warming the stomach, dispelling cold, relieving pain, regulating qi, stopping vomiting, and alleviating diarrhea.And, A. officinarum is commonly used to treat epigastric cold pain, vomiting, diarrhea, and food stagnation.
A. officinarum has been widely used in clinics due to its compatibility in many prescriptions, as shown in Table 2. A. officinarum is mainly used to warm the spleen and stomach, such as in Er Jiang Pill (Liu, 2017), which can nourish the spleen and stomach, remove cold, and eliminate phlegm, and cure all injuries caused by cold.Such prescriptions also include Wenzhong Liangjiang Pill (Liu, 2017) and Qing Zao San (Zhu, 2003).A. officinarum is a pungent and hot substance that is a pure yang product.It enters the spleen and stomach meridians, which can warm the stomach, reduce reflux and stop vomiting, and strengthen the spleen and stop diarrhea.For example, Ding Qi San (Zhao, 2018) is suitable for vomiting induced by typhoid.This type of prescription also includes Bi Cheng Qie San (Dou, 2015).A. officinarum can also enter the heart and Dan zhong, so it can enter the heart and pericardial meridian to warm and circulate qi.The prescriptions suitable for these kinds of conditions are Liang Fu Pill (Xie, 1990) and Gao Liang Jiang Decoction (Sun, 1955).With its fragrant and warm properties, A. officinarum can dissipate the cold, relieve pain, and promote qi.For example, Tian Tai Wu Yao San (Li, 1959) is applicable to the syndrome of cold coagulation and qi stagnation in the liver meridian.A. officinarum also has the effect of dispelling wind and relieving pain.The Qun Xun San, composed of A. officinarum and scorpion, has significant therapeutic effects on wind-induced toothache and swelling and pain in the cheek (Wang, 2003).In addition, A. officinarum has certain effects of warming the kidney and enhancing Yang. A. officinarum is compatible with Tetradium ruticarpum (A.Juss.) T. G. Hartley, which can warm the kidneys and dispel cold, and treat kidney deficiencies and waist pain.This type of prescription also includes Baji Pill (Liu, 2017).Frontiers in Pharmacology frontiersin.org03 Lei et al. 10.3389/fphar.2024.1414635have been isolated, including 18 flavones, 2 flavanones, and 1 flavanol, as shown in Figure 1 and Table 3.

Diarylheptanoids
Diarylheptanoid is a group of compounds that contain a 1,7disubstituted aromatic ring and a heptane skeleton and is an important chemical component of A. officinarum.At present, 49 diarylheptanoid compounds have been isolated from A. officinarum, including 42 chain diarylheptanoids, six cyclic diarylheptanoids, and one polymer of diarylheptanoid and flavonoid, as shown in Figure 2 and Table 4.

Volatile oil
A. officinarum is a type of pungent and warm botanical drugs with a high content of volatile oil.Its spicy scent is one of the indicators used to judge the quality of this herbal medicine.At present, 241 volatile oils have been separated from A. officinarum, mainly including terpenoids (monoterpenes, sesquiterpenoids), aldehydes, ketones, ethers, alcohols, phenols, and other compounds, as shown in Table 5.
In addition, a previous study (Xin Zhang et al., 2021) found that microemulsion can promote the absorption of galangin and improve its bioavailability.The blood concentration of galangin in Liangfu Pill could not be detected after the rabbits were given Liangfu Pill by gavage once.For Liangfu micromilk, the absorption half-life (t 1/2ka ) of galangin was 0.29 h, the peak time (t peak ) was 0.75 h, the elimination half-life (t 1/2ke ) was 1.47 h, C max was 38.46 μg/L, and the AUC was 129.42 (μg•h)/L.In another study (Xianhua Du et al., 2008), it was found that a self-microemulsion of galangin was absorbed throughout the entire intestinal tract of rats.The absorption rate constants (K a ) in the duodenum, jejunum, ileum, and colon were 2.37, 1.70, 2.29, and 3.98 times higher than those of the galangin suspension, respectively.Additionally, the apparent absorption coefficients (Papp) were 3.58, 2.56, 3.57, and 5.16 times higher than those of the galangin suspension, respectively.The relative bioavailability of the self-microemulsion of galangin was 220%, compared to the galangin suspension.

Pharmacological effects of A. officinarum
A. officinarum is an important traditional Chinese medicine, and its main chemical components are flavonoids, volatile oils, and diarylheptanoids.Modern pharmacological studies have shown that A. officinarum has various pharmacological effects, including anti-ulcer, inhibition of gastrointestinal motility, anti-inflammatory and analgesic, antioxidant, anti-tumor, antibacterial, and hypoglycemic properties, as shown in Table 7.

Effects on gastrointestinal function
A. officinarum is an essential medicine for treating deficiencycold of the spleen and stomach, as well as epigastric cold pain in traditional Chinese medicine.It is mainly used in the treatment of digestive tract diseases such as dyspepsia, acid reflux, and gastric ulcers.Wei (2019) used anhydrous ethanol and aspirin to induce two types of gastric ulcers models to study the effects of The results showed that the aqueous extract of A. officinarum had a good anti-ulcer effect and decreased the ulcer index.It was inferred that the mechanism of the anti-ulcer effect of A. officinarum may be through inhibiting inflammatory factors, reducing gastrin (GAS), increasing cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2), thereby enhancing the protective effect of the gastric mucosa and reducing gastric injury.Wang et al. (2011) studied the therapeutic effect of the volatile oil of A. officinarum on gastric ulcers.The results showed that the volatile oil of A. officinarum could reduce the gastric ulcer index and increase the ulcer inhibition rate in mice. A. officinarum reduces the levels of serum motilin (MOT) and substance P (SP), while increasing the levels of serum somatostatin (SS) and vasoactive intestinal peptide (VIP) in order to exert its anti-ulcer effect.In addition, the study found that the volatile oil of A. officinarum can increase the levels of serum nitric oxide (NO), expand the blood vessel walls, improve the microcirculation of the gastric mucosa, strengthen the mucosal barrier, scavenge oxygen free radicals, and protect the normal function of the gastric mucosa.
A. officinarum has an obvious gastrointestinal spasmolytic effect, and its decoction can inhibit gastrointestinal propulsive movement.Gui et al. (2021) observed the effect of the total flavonoids of A. officinarum on the propulsive movement of the small intestine in normal rats using the charcoal powder method.The results showed that the total flavonoids of A. officinarum not only significantly inhibited the intestinal motility of normal rats, but also antagonized the hyperfunction of the small intestine induced by neostigmine.The mechanism may be that it affects the secretion and release of gastrointestinal hormones, such as somatostatin and vasoactive intestinal peptide, thus relaxing the smooth muscle.Cheng Yuan et al. (Cheng et al., 2015) studied the effects of The structure of flavonoids in A. officinarum.Frontiers in Pharmacology frontiersin.org06 various active components of A. officinarum on intestinal spasms induced by acetylcholine and on normal intestinal muscles in isolated rabbits.The results showed that the active components of A. officinarum extract could inhibit the spontaneous movement of intestinal muscles in a dose-dependent manner.Among these components, flavonoids and diphenylheptanes were the most prominent, and they were stronger than anisodamine.The mechanism of A. officinarum in improving gastrointestinal function is shown in Figure 4.

Analgesic and anti-inflammatory effect
A. officinarum is hot and pungent, which has the effect of dispelling cold and relieving pain.As the use of non-steroidal anti-inflammatory drugs for long-term treatment of inflammation can cause obvious side effects, plants are constantly being developed as potential anti-inflammatory agents.Chen et al. (2009) used the carrageenan rat foot swelling model, the xylene mouse ear swelling model, and a capillary permeability experiment to study the antiinflammatory effect of the total flavonoids extracted from A. officinarum.The mouse hot plate method and torsion test were used to observe the analgesic effect of the total flavonoids extracted from A. officinarum.The results showed that the total flavonoids extracted from A. officinarum had a significant inhibitory effect on acute inflammation models, such as toe swelling induced by carrageenan, auricle swelling induced by xylene, and an increase in celiac capillary permeability induced by acetic acid in mice.The total flavonoids of A. officinarum can inhibit pain induced by acetic acid and heat stimulation in mice.Liang et al. (2013) studied the therapeutic and analgesic effects of total flavonoids from A. officinarum (GLJ) on acetic acid-induced visceral hypersensitivity in rats with irritable bowel syndrome (IBS).The results showed that GLJ had a certain inhibitory effect on pain induced by heat stimulation, acetic acid, and formaldehyde in mice.Zha Wangjian et al. (Cha, 2015) found that galangin can inhibit airway inflammation and airway hyperresponsiveness to some extent in a mouse model of asthma.In addition, A. officinarum and its main compounds have anti-inflammatory effects on LPSinduced inflammation in RAW264.7 cells.This may be related to the inhibition of NF-κB activation.The anti-inflammatory mechanism of the total flavonoids of A. officinarum is shown in Figure 5A.

Antioxidant effect
An antioxidant is a type of active substance that can eliminate the inhibition of lipid peroxidation by free radicals.It can prevent Frontiers in Pharmacology frontiersin.org07 Lei et al. 10.3389/fphar.2024.1414635 TABLE 4 The structure of diarylheptanoids in A. officinarum.
Frontiers in Pharmacology frontiersin.org13 inhibiting reactive oxygen free radicals and decreasing the catalytic activity of metal ions in vitro.In the HepG2 oxidative damage model induced by H 2 O 2 , diphenylheptane in A. officinarum showed significant antioxidant activity.The extract of A. officinarum could potentially prevent oxidative stress damage by activating the Keap1/Nrf2/ARE signaling pathway.The antioxidant mechanism of the extract of A. officinarum is shown in Figure 5B.

Antibacterial effect
The in vitro antibacterial experiment conducted by Zhao et al. (2007) showed that the chloroform and ethyl acetate extracts of A. officinarum exhibited anti-Candida albicans activity.The chloroform extract of A. officinarum, at a concentration of 20 mg/mL, demonstrated strong activity.Qin et al. (2015) showed that both the alcohol extract and water extract of A. officinarum had a good inhibitory effect on methicillin-resistant Staphylococcus aureus, but had no significant inhibitory effect on Pseudomonas aeruginosa, Candida albicans, Acinetobacter, or Escherichia coli.Flavonoids are the most important antibacterial components of A. officinarum.Ouyang et al. (2018) studied the impact of galangin on the antibacterial activity against vancomycinintermediate S. aureus.The study results showed that galangin had significant inhibitory activity against ATCC25293, N315, and Mu50, with a minimum inhibitory concentration (MIC) of 32 mg/L.The results of further studies showed that galangin inhibited the growth of bacteria by inhibiting the activity of cell wall hydrolase.At the same time, the effect of quercetin on P. aeruginosa PAO1 was also studied (Ouyang et al., 2016).The results showed that 16 mg/L of quercetin could significantly inhibit the biofilm formation, the quorum sensing system, and independent factors of P. aeruginosa.This suggests that quercetin may have the potential to treat biofilm-associated infections.

Improve memory ability
Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system in middle-aged and elderly individuals.Its main clinical manifestation is cognitive dysfunction.Huang Liping (Huang et al., 2022) has shown that galangin can improve learning and memory impairment in APP/PS1 mice.It may inhibit the activity of acetylcholinesterase (AChE) in the brain through the cholinergic pathway, increasing the level of ACh and improving learning and memory function.On the other hand, it may play a role in protecting hippocampal neurons by regulating the Akt/MEF2D/ Beclin-1 signaling pathway and clearing abnormal proteins in  Frontiers in Pharmacology frontiersin.org14 Lei et al. 10.3389/fphar.2024.1414635

Anti-tumor effect
The anti-tumor mechanism of A. officinarum can be reflected in regulating the cell cycle, inducing tumor cell apoptosis and autophagy, inhibiting tumor cell migration and invasion, and reversing drug resistance in tumors.Luo and Liu (2020) found that galangin has a broad-spectrum anti-tumor effect.Its inhibitory effect on different tumor cells varies and depends on time and concentration.Galangin can strongly inhibit the genotoxicity of chemical toxic substances in vivo and in vitro, making it a potential preventive drug for cancer.

Other functions
In addition to the above pharmacological effects, A. officinarum has anti-liver injury, hypoglycemic, hypolipidemic, and anticoagulant effects.Zhou et al. (2012) showed that A. officinarum can protect the function of hepatocytes in mice after an acute alcoholic liver injury.The results showed that A. officinarum could significantly reduce the concentrations of alanine aminotransferase (ALT) and aspartate transaminase (AST) in the serum of mice after injury, indicating that A. officinarum has a certain hepatoprotective effect.Its pharmacological mechanism may be to protect liver cells by scavenging free radicals and reducing the degree of damage caused by alcohol.Akhtar et al. (2002) showed that the extract of A. officinarum has a significant hypoglycemic effect.In the hypoglycemic experiment on normal male New Zealand rabbits, oral A. officinarum powder at a dose of 3 g/kg significantly reduced blood glucose levels.The methanol and water extracts showed even more pronounced hypoglycemic effects.When the oral dose was increased to 4 g/kg, there was a significant decrease in blood glucose levels of rabbits after 8 h.However, A. officinarum powder and its extract had no effect on rabbits with diabetes induced by alloxan.Therefore, its hypoglycemic effect may be achieved by promoting insulin secretion from the pancreas in the body.Obese patients are often accompanied by abnormal fat metabolism, which can lead to high blood total cholesterol (TC) and/or triglyceride (TG) levels.Fang et al. (2015) showed that middle and high doses of total flavonoids from A. officinarum play a significant role in controlling body mass, fat accumulation, and cholesterol metabolism, as well as reducing the levels of serum leptin and plasma neuropeptide Y in nutritionally obese rats with hyperlipidemia.A study (Luo et al., 2015) has shown that galangin has an obvious inhibitory effect on thrombosis in rats, demonstrating a certain anticoagulant effect.The potential mechanism may be to improve the blood flow state of rats by participating in the endogenous coagulation system.

Conclusion and prospection
A. officinarum is an important traditional Chinese medicine for both medicine and food.Using modern research methods, the pharmacological effects of its active compounds have been clearly The mechanism of A. officinarum in improving gastrointestinal function.Toll-like receptor 4 (TLR4), nerve growth factor (NGF), calcitonin generelated peptide (CGRP), gastric ulcer (GU).
described, and the mechanisms of anti-gastric ulcer, inhibition of gastrointestinal motility, antioxidant effect, antibacterial, antiinflammatory, and analgesia have been gradually clarified.The treatment of traditional digestive tract diseases has been expanded to a certain extent, broadening its scope of clinical application.So far, 337 compounds have been isolated from A. officinarum.Among them, galangin is a very important active compound extracted from A. officinarum.The pharmacological effects of galangin are very extensive.However, most pharmacological effects are currently only verified in cell and animal models, and there is a lack of clinical study data to support them.In addition, the mechanism of pharmacological action of galangin is not fully understood.Most studies are limited to the pharmacodynamic level or a few specific targets or pathways, and are unable to elucidate the general mechanism of action or the connection between the various targets and pathways.In the future, based on existing research, network pharmacology, bioinformatics, and multi-omics analysis can be used to comprehensively and deeply analyze the molecular mechanisms, genes, and signaling pathways of galangin.Further studies are needed to explore the extracts of A. officinarum for any potential toxicities, side effects, and contraindications.With the continuous discovery of the structure of the active components of A. officinarum and the in-depth study of its pharmacological activity, its pharmacodynamic mechanism is gradually becoming clear.The research scope of the pharmacological activity of A. officinarum has been continuously expanded by the vast number of scientific research works, and its medicinal value will be further developed and applied.

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FIGURE 2
FIGURE 2Structure of diarylheptanoids in A. officinarum.

TABLE 1
Medicinal properties, meridian tropism, and efficacy of A. officinarum.
(Continued on following page)

TABLE 2
Prescription name, composition and therapeutic application of A. officinarum.

TABLE 3
The flavonoids of A. officinarum.

TABLE 5
Volatile oil from A. officinarum.
Xia et al. (2009)lowing page)Frontiers in Pharmacology frontiersin.orgthedamagecausedbylipid peroxidation to organisms.In a comparative study on the antioxidant activity of various components of A. officinarum extract,Lin et al. (2017)discovered that the diphenylheptanes exhibited antioxidant activity both in vitro and in vivo.Xia et al. (2009)found that the total flavonoids of A. officinarum can act as antioxidants by

TABLE 6
Other compounds in A. officinarum.

TABLE 7
Study on pharmacological effects of A. officinarum.

TABLE 7 (
Continued) Study on pharmacological effects of A. officinarum.

TABLE 7 (
Continued) Study on pharmacological effects of A. officinarum.

TABLE 7 (
Continued) Study on pharmacological effects of A. officinarum.

TABLE 7 (
Continued) Study on pharmacological effects of A. officinarum.
(Zhai et al., 2014b)xtract can significantly reduce the lactate dehydrogenase leakage rate, decrease the content of MDA, and increase the activities of SOD and GSH-Px(Zhai et al., 2014b).

TABLE 7 (
Continued) Study on pharmacological effects of A. officinarum.